cardiovascular-agents and No-Reflow-Phenomenon

Coronary slow flow (CSF) is an angiographic phenomenon with specific epidemiologic characteristics, associated clinical presentation, and prognosis. Although patients with CSF are diagnosed as having "normal coronary arteries," it seems appropriate to consider CSF as a distinct disease entity requiring specific treatment. The patient with CSF is usually male, smoker, obese, with a constellation of risk factors suggestive of metabolic syndrome. Unstable angina is the most common clinical presentation, with recurrent episodes of chest pain at rest associated with electrocardiographic changes often requiring readmission and reevaluation. Regarding definition and diagnosis, interventionists should first exclude possible "secondary" causes of CSF, use objective means for definition and then differentiate from other similar conditions such as microvascular angina. Although the phenomenon is generally benign, patients with CSF are severely symptomatic with recurrent episodes of chest pain and poor quality of life. Furthermore, acute presentation of the phenomenon is commonly life-threatening with ventricular tachyarrhythmias, conduction abnormalities, or cardiogenic shock. Acute treatment of CSF includes, but is not restricted to, intracoronary infusion of dipyridamole, adenosine, or atropine. Chronic management of patients with CSF encompasses dipyridamole, diltiazem, nebivolol, telmisartan, and/or atorvastatin associated with amelioration of angina symptoms, improved quality of life, and good prognosis.

Topics: Blood Flow Velocity; Cardiovascular Agents; Coronary Angiography; Coronary Circulation; Humans; No-Reflow Phenomenon; Quality of Life; Risk Factors; Treatment Outcome

Thrombolytic therapy and revascularization strategies create a complete recanalization of the occluded epicardial coronary artery in patients with myocardial infarction (MI). However, about 35 % of patients still experience an impaired myocardial reperfusion, which is termed a no-reflow phenomenon mainly caused by cardiac microvascular ischemia-reperfusion (I/R) injury. Mitochondria are essential for microvascular endothelial cells' survival, both because of their roles as metabolic energy producers and as regulators of programmed cell death. Mitochondrial structure and function are regulated by a mitochondrial quality control (MQC) system, a series of processes including mitochondrial biogenesis, mitochondrial dynamics/mitophagy, mitochondrial proteostasis, and mitochondria-mediated cell death. Our review discusses the MQC mechanisms and how they are linked to cardiac microvascular I/R injury. Additionally, we will summarize the molecular basis that results in defective MQC mechanisms and present potential therapeutic interventions for improving MQC in cardiac microvascular I/R injury.

Topics: Animals; Apoptosis; Cardiovascular Agents; Coronary Circulation; Energy Metabolism; Humans; Microcirculation; Mitochondria, Heart; Mitochondrial Dynamics; Mitophagy; Myocardial Reperfusion Injury; Myocytes, Cardiac; Necrosis; No-Reflow Phenomenon; Organelle Biogenesis; Signal Transduction; Unfolded Protein Response

The coronary circulation is both culprit and victim of acute myocardial infarction. The rupture of an epicardial atherosclerotic plaque with superimposed thrombosis causes coronary occlusion, and this occlusion must be removed to induce reperfusion. However, ischaemia and reperfusion cause damage not only in cardiomyocytes but also in the coronary circulation, including microembolization of debris and release of soluble factors from the culprit lesion, impairment of endothelial integrity with subsequently increased permeability and oedema formation, platelet activation and leucocyte adherence, erythrocyte stasis, a shift from vasodilation to vasoconstriction, and ultimately structural damage to the capillaries with eventual no-reflow, microvascular obstruction (MVO), and intramyocardial haemorrhage (IMH). Therefore, the coronary circulation is a valid target for cardioprotection, beyond protection of the cardiomyocyte. Virtually all of the above deleterious endpoints have been demonstrated to be favourably influenced by one or the other mechanical or pharmacological cardioprotective intervention. However, no-reflow is still a serious complication of reperfused myocardial infarction and carries, independently from infarct size, an unfavourable prognosis. MVO and IMH can be diagnosed by modern imaging technologies, but still await an effective therapy. The current review provides an overview of strategies to protect the coronary circulation from acute myocardial ischaemia/reperfusion injury. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.

Topics: Animals; Cardiovascular Agents; Collateral Circulation; Coronary Circulation; Humans; Ischemic Postconditioning; Ischemic Preconditioning; Ischemic Preconditioning, Myocardial; Microcirculation; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Neovascularization, Physiologic; No-Reflow Phenomenon; Treatment Outcome

Currently, there is still a lack of an optimal treatment for no reflow phenomenon (NRP). We analyzed the efficacy and safety of using nondihydropyridine calcium channel antagonists (NDHP, verapamil/diltiazem) in patients suffering from NRP. Eight RCTs with 494 participants were eligible for analysis. The pooling analysis showed that intracoronary verapamil/diltiazem injection significantly decreased the occurrence of the coronary NRP (RR: 0.3, 95% CI: 0.16-0.57; P = 0.0002) and reduced corrected thrombolysis in myocardial infarction (TIMI) frame Count (WMD = -9.24, 95% CI -13.91-4.57; P = 0.0001) in patients with NRP. Moreover, verapamil/diltiazem treatment showed superiority in reducing wall motion index (WMI) compared to the control at day 1 (WMD = 0.11, 95% CI: 0.02-0.20; P = 0.02) (P < 0.05). There was also a significantly greater decline at occurrence of the major adverse cardiac events between verapamil/diltiazem and control groups (WMD: 0.4, 95% CI: 0.19-0.84; P = 0.02). However, using verapamil/diltiazem did not provide additional improvement of left ventricular ejection fraction post procedure (at 7 days, WMD, 0.1; 95% CI, -2.43-2.63; P = 0.94; at 30 days, WMD, 0.42; 95% CI, -2.09-2.92; P = 0.75). NDHP use is beneficial in attenuating NRP and reducing 6-month MACEs in patients with NRP.

Topics: Calcium Channel Blockers; Cardiovascular Agents; Diltiazem; Humans; No-Reflow Phenomenon; Randomized Controlled Trials as Topic; Verapamil

No-reflow phenomenon is a consequence of percutaneous coronary intervention (PCI) which arises most of the time in the setting of myocardial infarction, but can be also the consequence of PCI in stable angina patients (rotatablator ablation technique or angioplasty in saphenous vein grafts). In this review, we summarize two ways of treating the no-reflow according to the current literature. First through the pharmacological approach where several compounds have been assessed like adenosine, nitroprusside, verapamil, nicorandil, dipyridamole, epinephrine or cyclosporine. Second through the mechanical approach where few strategies have been examined like intra-aortic balloon pumping or postconditioning. Finally, we provide an algorithm for treating a no-reflow even though no studies showed a beneficial effect in terms of clinical endpoints.

Topics: Animals; Cardiovascular Agents; Humans; Ischemic Postconditioning; Myocardial Infarction; No-Reflow Phenomenon; Treatment Outcome

In a variant proportion of patients presenting with chest pain and electrocardiographic changes characteristic for ST - elevation myocardial infarction, percutaneous coronary intervention achieves epicardial coronary artery reperfusion but not the myocardial reperfusion (ranging from 5% to 50%). Furthermore, prolonged myocardial ischemia often breaks down the coronary microvasculature and the flow to the infarct myocardium may seem to be markedly reduced. This condition is known as no reflow - phenomenon. The no reflow - phenomenon is associated with an increased incidence of malignant ventricular arrhythmias, heart failure and 30-days mortality. In the recent years in literature, several articles (subsequently discussed in the present review) have been published and made relevant to the study of the pathophysiology regarding no reflow - phenomenon. This knowledge has assisted in the development of new treatment strategies, such as prophylactic use of vasodilators, mechanical devices and drugs inhibiting platelet. The review has focused on the current literature about intra - coronary injection of drugs to treat no - reflow and microvascular dysfunction.

Topics: Cardiovascular Agents; Coronary Circulation; Humans; Injections; Microcirculation; Myocardial Infarction; No-Reflow Phenomenon

The no-reflow phenomenon (NRP) is defined as the lack of adequate myocardial tissue perfusion despite a patent epicardial coronary artery. The incidence of NRP varies between 2-5% of elective percutaneous coronary interventions (PCI) and 30% in primary PCI. Clinically, it is an independent predictor of myocardial infarction, in-hospital mortality, and long-term mortality. It may be categorized in interventional (after PCI, especially in saphenous venous grafts) or reperfusion NRP (after re-opening of a totally occluded coronary artery, usually during primary PCI or thrombolysis). There are many physiopathological factors implicated: distal microembolization, interstitial and intracellular edema, coronary spasm and capillary plugging. Although reperfusion and no reflow is a field of intense research, no single mechanical or pharmacological therapy has demonstrated a clear efficacy against NRP, probably due to its multifactorial nature. Once established, the treatment of NRP is based on vasodilators like adenosine, verapamil, nitroprusside or nicorandil. However, the efficacy of these measures is poor, so every effort should be made to prevent the apparition of NRP. The objective of this report is to provide an update of the pharmacological armamentarium available for the prevention and treatment of NRP, and suggest a systematic approach of the management of NRP according to the different possible clinical scenarios.

Topics: Cardiovascular Agents; Chemistry, Pharmaceutical; Humans; No-Reflow Phenomenon

These studies sought to investigate the impact on mortality of coronary flow after passage of the wire through the culprit vessel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical reperfusion.. Reduced spontaneous coronary flow before percutaneous coronary intervention influences mortality in patients with STEMI. Response to vessel wiring in patients with an occluded coronary artery before intervention might further discriminate outcomes irrespective of pre- and post-intervention coronary flow.. Data from the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) trials were pooled: of 919 index procedures, 902 films (98%) were technically adequate for core laboratory TIMI (Thrombolysis In Myocardial Infarction) flow determination.. TIMI flow grade 0 was present before percutaneous coronary intervention in 59% of infarct vessels, TIMI flow grade 1 to 2 was found in 21%, whereas the remainder of infarct arteries presented with TIMI flow grade 3. In 49% of patients who showed persistent TIMI flow grade 0 after wire insertion (AWI), mortality was higher at 30 days (5.3%) and 1 year (9.4%) compared with patients in whom TIMI flow grade before percutaneous coronary intervention was either >0 (0.8%; p < 0.003 and 3.6%, p < 0.008) or improved from 0 AWI (1.5%, p < 0.04 and 3.6%, p < 0.02). After correcting for multiple imbalances, including baseline and final flow, persistent TIMI flow grade 0 AWI remained associated at 30 days to 2-fold (risk ratio [RR]: 2.1, 95% confidence interval [CI]: 1.08 to 5.00; p = 0.038) and at 1 year to almost 3-fold increases of mortality (RR: 2.7, 95% CI: 1.3 to 5.6; p = 0.008).. STEMI patients displaying persistent no-flow AWI have a lower survival rate despite an apparently successful mechanical intervention. As an early marker for high residual mortality risk, persistent no-flow AWI may qualify STEMI patients for dedicated pharmacomechanical treatment strategies.

Topics: Abciximab; Aged; Analysis of Variance; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Cardiovascular Agents; Coronary Angiography; Coronary Circulation; Drug-Eluting Stents; Evidence-Based Medicine; Female; Humans; Immunoglobulin Fab Fragments; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; No-Reflow Phenomenon; Platelet Aggregation Inhibitors; Predictive Value of Tests; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Sirolimus; Stents; Time Factors; Tirofiban; Treatment Outcome; Tyrosine

Microvascular obstruction (MVO) commonly occurs following percutaneous coronary interventions (PCI), may lead to myocardial injury, and is an independent predictor of adverse outcome. Severe MVO may manifest angiographically as reduced flow in the patent upstream epicardial arteries, a situation that is termed "no-reflow." Microvascular obstruction can be broadly categorized according to the duration of myocardial ischemia preceding PCI. In "interventional MVO" (e.g., elective PCI), obstruction typically involves myocardium that was not exposed to acute ischemia before PCI. Conversely "reperfusion MVO" (e.g., primary PCI for acute myocardial infarction) occurs within a myocardial territory that was ischemic before the coronary intervention. Interventional and reperfusion MVO have distinct pathophysiological mechanisms and may require individualized therapeutic approaches. Interventional MVO is triggered predominantly by downstream embolization of atherosclerotic material from the epicardial vessel wall into the distal microvasculature. Reperfusion MVO results from both distal embolization and ischemia-reperfusion injury within the subtended ischemic tissue. Management of MVO and no-reflow may be targeted at different levels: the epicardial artery, microvasculature, and tissue. The aim of the present report is to advocate a systematic approach to prevention and treatment of MVO in different clinical settings. Randomized clinical trials have studied strategies for prevention of MVO and no-reflow; however, the efficacy of measures for reversing MVO once no-reflow has been demonstrated angiographically is unclear. New approaches for prevention and treatment of MVO will require a better understanding of intracellular cardioprotective pathways such as the blockade of the mitochondrial permeability transition pore.

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Circulation; Embolism; Evidence-Based Medicine; Filtration; Humans; Ischemic Preconditioning, Myocardial; Microcirculation; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; No-Reflow Phenomenon; Treatment Outcome

It is controversial as to whether nicorandil would have cardioprotective effects in patients with acute myocardial infarction (AMI) who are undergoing reperfusion therapy. A meta-analysis was performed to study the impacts of nicorandil on functional outcomes after AMI.. Randomized prospective cohort or retrospective cohort publications were identified up to October 2007 by means of a computer search of MEDLINE and Google Scholar databases. Two reviewers checked the quality of the studies and extracted data regarding patient and disease characteristics, study design, functional parameters such as Thrombolysis In Myocardial Infarction (TIMI) flow grade after reperfusion, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume index (LVEDVI). Seventeen studies were included for the meta-analysis in this study. Nicorandil treatment reduced the incidence of TIMI flow grade < or =2 in 1,337 patients of 10 studies (risk ratio 0.63; 95% confidence interval (CI) 0.44 to 0.91). While no beneficial effect was observed on the peak creatine kinase value, nicorandil treatment was associated with greater LVEF (by 3.7%, 95%CI 1.8 to 5.7%), and lower LVEDVI (by 8.8 ml/kg, -14.4 to -3.3 ml/kg) in 905 patients of 11 studies.. The meta-analysis demonstrated that nicorandil treatment adjunctive to reperfusion therapy has beneficial effects on microvascular function and on functional recovery after AMI.

Topics: Aged; Cardiovascular Agents; Combined Modality Therapy; Coronary Circulation; Female; Humans; Male; Microcirculation; Middle Aged; Myocardial Infarction; Myocardial Reperfusion; Nicorandil; No-Reflow Phenomenon; Publication Bias; Recovery of Function; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Successful reopening of epicardial coronary artery does not always mean optimal myocardial reperfusion in a sizable portion of patients, mostly because of no-reflow phenomenon.. We investigated whether local injection of adrenaline ± verapamil in the distal coronary bed is more effective than their intracoronary (IC) injection through the guiding catheter in the treatment of no-reflow phenomenon following percutaneous coronary intervention (PCI).. A total of 40 patients with no-reflow following PCI were randomized into two groups. Group 1 received IC adrenaline ± verapamil through a well-cannulated guiding catheter while Group 2 received the above-mentioned drugs in the distal coronary bed through a perfusion balloon or selective microcatheter. The primary end points were the achievement of TIMI III flow with MBG II or III. Secondary end points were the occurrence of hypotension, arrhythmias, and major adverse cardiac events (MACEs) during hospital stay.. After drug injection, the percentage of patients achieving Thrombolysis in Myocardial Infarction (TIMI) III flow in Group 1 was 40% versus 80% in Group 2, P = 0.032. MBG II and III was significantly lower in Group 1; 10% and 25% versus 15% and 65% in Group 2, respectively, P = 0.033. Primary end points were achieved in only 35% of patients in Group 1 and in 80% of patients in Group 2 (odds ratio, 7.43, 95% confidence interval 1.78-31.04, P < 0.01). Secondary end points were not different between both groups.. Local intra-coronary delivery of adrenaline ± verapamil is a safe and effective method for the treatment of no-reflow phenomenon complicating PCI.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Vessels; Epinephrine; Female; Humans; Injections, Intra-Arterial; Male; Middle Aged; Myocardial Reperfusion; No-Reflow Phenomenon; Pilot Projects; Treatment Outcome; Verapamil

Slow flow, no reflow and distal embolization often occur during primary angioplasty in ST segment elevation myocardial infarction (STEMI), compromising optimal myocardial reperfusion.. This study aimed at assessing the impact of deferred stenting (DS) on periprocedural events as compared to immediate stenting (IS). The second objective was to gather the reasons advocated by the physicians for deferring stenting.. All consecutive patients referred for primary angioplasty were included between September 2010 and November 2011. Physicians were free to choose the strategy between DS and IS but had to justify their choice. DS patients underwent a coronary angiogram control in a delay > 24h.. Ninety-eight patients were included. Forty patients underwent DS and 58 IS. DS strategy involved thrombus management by thromboaspiration (33 patients 82.5%) and by the use of AntiGpIIbIIIa (23 patients 62.2%). This strategy could be achieved with a low complication rate. In particular, one patient had a reocclusion leading to a rapid reintervention and one had a distal embolization. In comparison, 11 periprocedural events occurred in the IS subgroup. In addition, among DS patients, 7 were treated medically because of a non-significant stenosis. The major criteria considered by the operator to prefer DS in the presence of a TIMI 3 flow concerned thrombotic load.. This mono-centric experience confirmed the feasibility and the safety of DS. On top of reducing periprocedural events, it may allow for other treatment options in selected STEMI patients, e.g. surgery or medical treatment. The reasons leading physicians to choose DS were large thrombus burden on top of resolution of chest pain and normalization of the ECG. These criteria could help selecting situations in which DS may be of particular value as compared to IS.

Topics: Adult; Aged; Aged, 80 and over; Cardiac Catheterization; Cardiovascular Agents; Chest Pain; Comorbidity; Coronary Angiography; Coronary Thrombosis; Electrocardiography; Embolism; Feasibility Studies; Female; Heart Arrest; Hemorrhage; Hospital Mortality; Humans; Male; Middle Aged; Motivation; Myocardial Infarction; No-Reflow Phenomenon; Percutaneous Coronary Intervention; Physicians; Risk Factors; Shock, Cardiogenic; Stents; Thrombectomy; Time Factors

The "no reflow" phenomenon, where the coronary artery is patent after treatment of acute myocardial infarction (AMI) but tissue perfusion is not restored, is associated with worse outcome. The mechanism of no reflow is unknown. We hypothesized that pericytes contraction, in an attempt to maintain a constant capillary hydrostatic pressure during reduced coronary perfusion pressure, causes capillary constriction leading to no reflow and that this effect is mediated through the orphan receptor, GPR39, present in pericytes. We created AMI (coronary occlusion followed by reperfusion) in GPR39 knock out mice and littermate controls. In a separate set of experiments, we treated wild-type mice undergoing coronary occlusion with vehicle or VC43, a specific inhibitor of GPR39, before reperfusion. We found that no reflow zones were significantly smaller in the GPR39 knockouts compared with controls. Both no reflow and infarct size were also markedly smaller in animals treated with VC43 compared with vehicle. Immunohistochemistry revealed greater capillary density and larger capillary diameter at pericyte locations in the GPR39-knockout and VC43-treated mice compared with controls. We conclude that GPR39-mediated pericyte contraction during reduced coronary perfusion pressure causes capillary constriction resulting in no reflow during AMI and that smaller no reflow zones in GPR39-knockout and VC43-treated animals are associated with smaller infarct sizes. These results elucidate the mechanism of no reflow in AMI, as well as providing a therapeutic pathway for the condition.

Topics: Animals; Calcium Signaling; Cardiovascular Agents; Cells, Cultured; Coronary Circulation; Coronary Vessels; Disease Models, Animal; Female; Male; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction; No-Reflow Phenomenon; Pericytes; Receptors, G-Protein-Coupled; Vasoconstriction

A 78-year-old man with unstable angina showed 90% stenosis in the proximal left anterior descending artery. Pre-procedural intravascular ultrasound revealed ruptured plaque and attenuated plaque in the lesion. Under these conditions, two overlapping sirolimus-eluting stent (SES) implantation in this lesion resulted in slow flow which was recovered by intracoronary nitrates, nicorandil, and nitroprusside without further complications. When the patient showed up again 5 years later with recurrence of angina pectoris, angiography revealed a hazy ulcerated in-stent restenosis (ISR) at the site of the SES. Pre-procedural optical coherence tomography (OCT) imaging revealed multiple intimal ruptures, cavity formation behind the stent struts, a thin-cap fibroatheroma containing neointima surrounded by signal-poor, lipid-rich area in the proximal SES, suggesting the progression of neoatherosclerosis within SES. Importantly, there occurred slow flow again after balloon angioplasty for this lesion. We would suggest careful OCT examination is warranted to confirm development of neoatherosclerosis within the stent, and distal protection device should be considered to prevent slow flow phenomenon even in a patient with very late ISR.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Circulation; Coronary Restenosis; Coronary Stenosis; Denture, Partial, Temporary; Drug-Eluting Stents; Humans; Male; No-Reflow Phenomenon; Recurrence; Retreatment; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Circulation; Coronary Occlusion; Drug-Eluting Stents; Evidence-Based Medicine; Humans; Metals; Myocardial Infarction; No-Reflow Phenomenon; Platelet Aggregation Inhibitors; Predictive Value of Tests; Risk Assessment; Risk Factors; Stents; Treatment Outcome

We report the case of a 55-year-old man who presented with acute coronary syndrome due to coronary slow flow after spinal cord injury. Data regarding the causes and clinical manifestations of coronary slow flow are inconclusive, but the autonomic nervous system is believed to be at least a contributing factor. The predominant vagal activity causes vasodilation and hemostasis, which can lead to acute coronary syndrome. We hereby call attention to hyperactive parasympathetic tonicity, which can lead to coronary slow flow and acute coronary syndrome in acute spinal cord injury patients.

Topics: Acute Coronary Syndrome; Cardiovascular Agents; Coronary Angiography; Coronary Circulation; Electrocardiography; Hemostasis; Humans; Magnetic Resonance Imaging; Male; Middle Aged; No-Reflow Phenomenon; Physical Therapy Modalities; Spinal Cord Injuries; Treatment Outcome; Vagus Nerve; Vasodilation

Topics: Cardiovascular Agents; Contrast Media; Coronary Angiography; Hemodynamics; Humans; Male; Middle Aged; No-Reflow Phenomenon; Treatment Outcome

The cardioprotective property of Spondias mombin (SM) was investigated and compared with that of the ACE inhibitor, ramipril. Alterations to markers of myocardial injury and indices of antioxidant capacity by isoproterenol (ISP) intoxication were significantly corrected in groups treated with SM. The inflammatory index was increased by 24% in ISP-intoxicated group compared with control (P < 0.001) but reduced in the groups administered ISP and treated with 100 or 250 mg/kg SM by 17% (P < 0.001) and 11% (P < 0.05) respectively. Serum lactate dehydrogenase activity and cholesterol level which were significantly increased in ISP-intoxicated group compared with control were reduced in groups administered ISP and treated with SM. Serum phosphate levels in groups administered ISP and treated with SM were significantly lower than values obtained for the ISP-intoxicated group (P < 0.001). Tissue catalase and superoxide dismutase activities as well as glutathione level were significantly increased in groups administered ISP and treated with SM compared to ISP-intoxicated group while MDA and nitrite levels were decreased. Disruption in the structure of cardiac myofibrils by ISP intoxication was reduced by treatment with SM. Comparable results were obtained for ramipril. These results are indicative of the potent cardioprotective property of SM.

Topics: Anacardiaceae; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiovascular Agents; Catalase; Cholesterol; Disease Models, Animal; Dose-Response Relationship, Drug; Glutathione; Isoproterenol; L-Lactate Dehydrogenase; Male; Malondialdehyde; Myocardial Infarction; Myocardial Ischemia; Myocardium; Nitrites; No-Reflow Phenomenon; Phosphates; Plant Extracts; Plant Leaves; Ramipril; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Time Factors

It has been suggested that ranolazine protects the ischemic/reperfused heart by reducing diastolic wall pressure during ischemia. However, there is limited information regarding the effect of ranolazine on the anatomic zone of no-flow in a model of acute myocardial occlusion/reperfusion. Before coronary artery occlusion (CAO), open-chest anesthetized rabbits were assigned to vehicle or ranolazine. Hearts received 60 minutes of CAO and 3 hours reperfusion. Ischemic risk zone was comparable in the 2 groups. Ranolazine significantly reduced infarct size. There was a non-significant trend for the no-reflow defect to be smaller in the ranolazine group. Regional myocardial blood flow was similar in both groups in the risk zone during ischemia and at 3 hours reperfusion. Heart rates were similar in both groups, whereas mean arterial pressure was reduced in the ranolazine group. While ranolazine was effective in reducing myocardial infarct size, the mechanism by which it did this was independent of improving perfusion during either ischemia or reperfusion, suggesting that ranolazine's effect of reducing infarct size involves alternative mechanisms.

Topics: Acetanilides; Animals; Blood Pressure; Cardiovascular Agents; Coronary Circulation; Disease Models, Animal; Heart Rate; Male; Myocardial Infarction; Myocardial Reperfusion Injury; No-Reflow Phenomenon; Piperazines; Rabbits; Ranolazine