pituitrin and Reperfusion-Injury

There has been considerable recent progress liver transplantation (LTX). The postreperfusion syndrome has clearly defined and typically responds to vasopressin and/or methylene blue when refractory to catecholamine therapy. Diastolic dysfunction and cirrhotic cardiomyopathy are prevalent and important in LTX recipients. The high cardiovascular risk and the increasing medical complexity of the current liver transplant recipient have stimulated the publication of guidelines for cardiovascular assessment before LTX. Cardiac surgery is increasingly more successful in patients with cirrhosis, including simultaneous heart-liver transplantation. Cardiopulmonary bypass in LTX is indicated for hemodynamic rescue and, at some centers, serves as the hemodynamic platform for liver implantation. Although acute renal injury is common after LTX, early diagnosis is now possible with novel biomarkers. Earlier detection of postoperative renal dysfunction may prompt intervention for renal rescue. The metabolic milieu in LTX remains critical. Regular insulin therapy may be more effective than infrequent large bolus therapy for potassium homeostasis. Careful titration of insulin therapy may improve freedom from severe hyperglycemia to decrease morbidity. Since the organization of dedicated anesthesia care teams for LTX improves perioperative outcome, this aspect of perioperative care is receiving systematic attention to optimize safety and quality. The specialty of LTX is likely to continue to flourish even more, given these pervasive advances.

Topics: Anesthesia; Cardiac Surgical Procedures; Humans; Kidney Diseases; Liver Transplantation; Methylene Blue; Postoperative Complications; Reperfusion Injury; Vasoconstrictor Agents; Vasoplegia; Vasopressins

Therapy of heart failure is more difficult when renal function is impaired. Here, we outline the effects on kidney function of the autacoid, adenosine, which forms the basis for adenosine A(1) receptor (A(1)R) antagonists as treatment for decompensated heart failure. A(1)R antagonists induce a eukaliuretic natriuresis and diuresis by blocking A(1)R-mediated NaCl reabsorption in the proximal tubule and the collecting duct. Normally, suppressing proximal reabsorption will lower glomerular filtration rate (GFR) through the tubuloglomerular feedback mechanism (TGF). But the TGF response, itself, is mediated by A(1)R in the preglomerular arteriole, so blocking A(1)R allows natriuresis to proceed while GFR remains constant or increases. The influence of A(1)R over vascular resistance in the kidney is augmented by angiotensin II while A(1)R activation directly suppresses renin secretion. These interactions could modulate the overall impact of A(1)R blockade on kidney function in patients taking angiotensin II blockers. A(1)R blockers may increase the energy utilized for transport in the semi-hypoxic medullary thick ascending limb, an effect that could be prevented with loop diuretics. Finally, while the vasodilatory effect of A(1)R blockade could protect against renal ischaemia, A(1)R blockade may act on non-resident cells to exacerbate reperfusion injury, where ischaemia to occur. Despite these uncertainties, the available data on A(1)R antagonist therapy in patients with decompensated heart failure are promising and warrant confirmation in further studies.

Topics: Adenosine; Animals; Heart Failure; Humans; Kidney; Kidney Tubules, Collecting; Kidney Tubules, Proximal; Receptors, Purinergic P1; Reperfusion Injury; Vasoconstriction; Vasopressins; Xanthines

Cardiovascular dysfunction in asphyxiated neonates contributes significantly to their morbidity and mortality. We have recently shown that a low-dose vasopressin infusion (0.005 - 0.01 units/kg per hour) may improve myocardial oxygen transport balance in a swine model of neonatal hypoxia-reoxygenation. We aimed to compare the systemic and regional hemodynamic effects of low-dose vasopressin to dobutamine, a synthetic beta-adrenoreceptor agonist. Piglets (1 - 5 days old, 1.6 - 2.2 kg) were anesthetized and instrumented to continuously monitor systemic hemodynamic parameters, including cardiac output and mesenteric flow indices. After 2 h of hypoxia (10% - 15% O2), piglets had normoxic reoxygenation for 4 h. In a blinded randomized fashion, piglets received infusion of either vasopressin (0.01 units/kg per hour started at 30 min of reoxygenation) or dobutamine (20 μg/kg per minute started at 2 h of reoxygenation) (n = 8 per group). Hypoxia-reoxygenation controls (placebo, n = 8) and sham-operated (n = 5) piglets were also studied. Tissue lactate, glutathione, glutathione disulfide, and lipid hydroperoxides levels and histology of the left ventricle and the small bowel were analyzed. Plasma was also analyzed for troponin-I and intestinal fatty acid-binding protein levels. Piglets subjected to hypoxia-reoxygenation had cardiogenic shock and metabolic acidosis, which improved on reoxygenation. During recovery, cardiac output and mesenteric flows gradually deteriorated and were increased similarly in vasopressin- and dobutamine-treated piglets (P < 0.05 vs. controls). Plasma troponin-I and left ventricular lactate levels were lower in the vasopressin and dobutamine groups (P < 0.05 vs. controls), with no difference in the histological analysis among groups. The intestinal GSSG/GSH ratio and lipid hydroperoxides level were lower in the vasopressin and dobutamine groups (P < 0.05 vs. controls). This study is the first to demonstrate that a low-dose vasopressin infusion used in the setting of neonatal swine model of hypoxia-reoxygenation is associated with an improvement in cardiac output and mesenteric perfusion.

Topics: Animals; Animals, Newborn; Asphyxia Neonatorum; Cardiac Output; Dobutamine; Glutathione; Heart Ventricles; Hypoxia; Lactic Acid; Lipid Peroxides; Mesenteric Artery, Superior; Oxygen; Reperfusion Injury; Shock, Cardiogenic; Swine; Troponin I; Vasopressins

The aim of the present study was to reveal the effect of liver ischemia–reperfusion injury (LIRI) on the activity of selected neuronal phenotypes in rat brain by applying dual Fos-oxytocin (OXY), vasopressin (AVP), tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT), corticoliberine (CRH), and neuropeptide Y (NPY) immunohistochemistry. Two liver ischemia–reperfusion models were investigated: (i) single ligation of the hepatic artery (LIRIa) for 30 min and (ii) combined ligation of the portal triad (the common hepatic artery, portal vein, and common bile duct) (LIRIb) for 15 min. The animals were killed 90 min, 5 h, and 24 h after reperfusion. Intact and sham operated rats served as controls. As indicated by semiquantitative estimation, increases in the number of Fos-positive cells mainly occurred 90 min after both liver reperfusion injuries, including activation of AVP and OXY perikarya in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, and TH, NPY, and PNMT perikarya in the catecholaminergic ventrolateral medullar A1/C1 area. Moreover, only PNMT perikarya located in the A1/C1 cell group exhibited increased Fos expression 5 h after LIRIb reperfusion. No or very low Fos expression was found 24 h after reperfusion in neuronal phenotypes studied. Our results show that both models of the LIRI activate, almost by the same effectiveness, a number of different neuronal phenotypes which stimulation may be associated with a complex of physiological responses induced by (1) surgery (NPY, TH, PNMT), (2) hemodynamic changes (AVP, OXY, TH, PNMT), (3) inflammation evoked by ischemia and subsequent reperfusion (TH), and (4) glucoprivation induced by fasting (NPY, PNMT, TH). All these events may contribute by different strength to the development of pathological alterations occurring during the liver ischemia–reperfusion injury.

Topics: Animals; Brain; Corticotropin-Releasing Hormone; Immunohistochemistry; Liver; Male; Neurons; Neuropeptide Y; Oxytocin; Phenotype; Phenylethanolamine N-Methyltransferase; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Reperfusion Injury; Tyrosine 3-Monooxygenase; Vasopressins

Previously we demonstrated that ANG II receptor (AT1R) blockade attenuates V2 receptor (V2R), AQP2, and pS256-AQP2 downregulation in the postobstructed kidney and partially reverses obstruction-induced inhibition of cAMP generation and cyclooxygenase 2 (COX-2) induction. Therefore, we speculated whether the effects of AT1R blockade on V2R and the vasopressin-regulated pathway are attributable to attenuated COX-2 induction. To examine this, rats were subjected to 24-h bilateral ureteral obstruction (BUO) followed by 48-h release and treated with the COX-2 inhibitor parecoxib or saline. Control rats were sham-operated. Parecoxib treatment significantly reduced urine output 24 h after release of BUO whereas urine osmolality and solute-free water reabsorption was comparable between saline- and parecoxib-treated BUO rats. Immunoblotting revealed a significant decrease in AQP2 and pS256-AQP2 abundance to 20 and 23% of sham levels in parecoxib-treated BUO rats compared with 40 and 55% of sham levels in saline-treated BUO rats. Immunohistochemistry confirmed the exacerbated AQP2 and pS256-AQP2 downregulation in parecoxib-treated BUO rats. Finally, parecoxib treatment had no effect on V2R downregulation and the inhibited, vasopressin-stimulated cAMP generation in inner medullary membrane fractions from the postobstructed kidney. In conclusion, COX-2 inhibition exacerbates AQP2 and pS256-AQP2 downregulation 48 h after release of 24-h BUO independently of V2R abundance and vasopressin-stimulated cAMP generation. The results indicate that COX-2 inhibition does not mimic AT1R blockade-mediated effects and that AT1R-mediated AQP2 regulation in the postobstructed kidney collecting duct is independent of COX-2 induction.

Topics: Adenylyl Cyclases; Animals; Aquaporin 2; Cyclooxygenase 2 Inhibitors; Down-Regulation; Isoxazoles; Kidney; Male; Phosphorylation; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Reperfusion Injury; Sodium-Potassium-Chloride Symporters; Solute Carrier Family 12, Member 1; Vasopressins

Hemodynamic instability may occur during liver transplantation especially following unclamping the portal vein. A period of hypotension (postreperfusion syndrome) is usually responsive to treatment with fluids, calcium, sodium bicarbonate, and vasoactive drugs, but if hypotension persists, other causes must be sought out. In this report, we present a case in which anaphylaxis, most likely due to a component of the University of Wisconsin preservation solution, occurred coincident with liver reperfusion and severely exacerbated reperfusion hemodynamic instability. To our knowledge, this is the first report of anaphylaxis at the time of reperfusion and may provide an explanation for cases of vasoplegic syndrome associated with graft reperfusion.

Topics: Alcoholism; Anaphylaxis; Bile; Blood Pressure; Dopamine; Hepatitis C, Chronic; Humans; Liver Transplantation; Male; Middle Aged; Phenylephrine; Reperfusion Injury; Respiration, Artificial; Treatment Outcome; Vasopressins

Transplantation of vital human organs is a lifesaving therapy for patients with end-stage organ failure who are medically fit to undergo the surgical procedure. However, deceased donor management remains one of the most neglected areas in transplantation medicine. Brainstem death leads to hemodynamic, metabolic, and immune consequences. Failure to recognize them and provide adequate physiological support accounts for loss of the scarce source of valuable donor organs. Donor optimization leads to increased organ procurement and contributes to improved organ function in the recipient. This article reviews the management advances and controversies of the brainstem-dead donor in an intensive care unit.

Topics: Brain Death; Brain Injuries; Humans; Kidney; Liver; Living Donors; Lung; Reperfusion Injury; Resuscitation; Thyroid Hormones; Tissue and Organ Procurement; Tissue Donors; Vasopressins

Kidney is thought to be a regenerative organ in terms of repair from acute tubular injury. It is unknown whether cell population contributes to repair disordered kidney. We attempted to identify and isolate highly proliferative cells from a single cell. We dissected a single nephron from adult rat kidney. Isolated nephrons were separated into segments and cultured. Outgrowing cells were replated after limiting dilution so that each well contained a single cell. One of cell line which was the most potent to grow was designated as rKS56. rKS56 cells showed cobblestone appearance and expressed immature cell markers relating to kidney development and mature tubular cell markers. rKS56 cells grew exponentially and could be maintained for 300 days without transformation. In different culture conditions, rKS56 cells differentiated into mature tubular cells defined by aquaporin-1, 2 expression, and responsiveness to parathyroid hormone or vasopressin. Engrafted to kidney in rat ischemic reperfusion model, rKS56 cells replaced in injured tubules in part after implantation and improved renal function. These results suggest rKS56 cells possess character such as self-renewal, multi-plasticity and capability of tissue repair. rKS56 may possibly contribute to the future development of cell therapy for renal regeneration.

Topics: Animals; Aquaporin 1; Aquaporin 2; Arginine Vasopressin; Cell Culture Techniques; Cell Differentiation; Cell Line; Cell Proliferation; Cells, Cultured; Cyclic AMP; Electrophoresis, Polyacrylamide Gel; Epithelial Cells; Immunoblotting; Karyotyping; Keratins; Kidney; Kidney Diseases; Kidney Tubules; Male; Microscopy, Fluorescence; Nephrons; Parathyroid Hormone; Phenotype; Rats; Rats, Sprague-Dawley; Regeneration; Renal Insufficiency; Reperfusion Injury; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stem Cells; Time Factors; Vasopressins

The effects of paraventricular nucleus (PVN) stimulation and vasopressin on gastric ischemia-reperfusion injury (GI-RI) were investigated in male SD rats of which the celiac artery was clamped for 30 min and reperfused for 1 h by removal of the clamp. The results were as follows. Both electrical and chemical stimulation of the PVN obviously attenuated the GI-RI. Bilateral electrolytic lesion of the nucleus tractus solitarius (NTS) or microinjection of AVP-V(1) receptor antagonist into the NTS could eliminate the protective effect of electrical stimulation of the PVN on GI-RI. Hypophysectomy did not influence the effect of electrical stimulation of the PVN. Both vagotomy and sympathectomy could increase the effect of stimulating PVN on GI-RI. Microinjection of arginine-vasopressin (AVP) into the PVN also attenuated the effect on GI-RI. These results suggest that the PVN and AVP participate in the regulation of GI-RI and play an important role in protection against GI-RI. This protective effect of PVN on GI-RI might be mediated by activation of AVP-ergic neurons in the PVN, which release AVP from the descending projection fibers and activate the AVP-V(1) receptors on the NTS neurons. The vagus and sympathetic nerves are involved in the efferent pathway exerting their effects on GI-RI. Hypophysis does not seem to be involved in the protective effect of PVN stimulation.

Topics: Afferent Pathways; Animals; Electric Stimulation; Male; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Stimulation, Chemical; Stomach; Sympathetic Nervous System; Vagus Nerve; Vasopressins