sodium-nitrite and Coronary-Disease

The time course of the effects of permanent myocardial ischemia without reperfusion on the coronary vascular endothelium and myocardium were investigated in anesthetized cats. The left anterior descending (LAD) coronary artery was occluded for 1.5, 3.0, 4.5, or 6.0 h. Coronary rings from the ischemic LAD and the nonischemic left circumflex (LCX) arteries were tested for their responsiveness to the endothelium-dependent vasodilators acetylcholine (ACh, 0.1-100 nM) and the calcium ionophore A23187 (1-1,000 nM), and the endothelium-independent vasodilator sodium nitrite (NaNO2, 0.1-100 microM). Vasorelaxation was not significantly impaired in response to ACh after 1.5 h of ischemia and only moderately impaired after 3.0 h of ischemia (63 +/- 5% of control). However, after 4.5 h of ischemia the ACh-induced response was decreased to 33 +/- 4% of control and further declined to 31 +/- 4% of control after 6.0 h (P less than 0.001 from 1.5 h). There was no significant decrease in LCX ring vasorelaxant responses to vasodilators at all times, and the LAD rings only showed a moderately decreased response to NaNO2 after 6.0 h of ischemia (82 +/- 4% relaxation, P less than 0.05). Transmission electron microscopy revealed very little endothelial damage at 4.5 and 6.0 h, with only some subendothelial swelling noted. Damage to the myocardium did not become significant until after 4.5 h of ischemia, and cardiac myeloperoxidase activity, indicative of neutrophil accumulation, was not significant at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acetylcholine; Animals; Arterial Occlusive Diseases; Calcimycin; Cats; Coronary Disease; Coronary Vessels; Creatine Kinase; Dose-Response Relationship, Drug; Endothelium, Vascular; In Vitro Techniques; Male; Microscopy, Electron; Muscle, Smooth, Vascular; Myocardium; Peroxidase; Sodium Nitrite; Vasodilation

The effects of acidified sodium nitrite (NaNO2) which releases nitric oxide, a substance which is thought to be indistinguishable from endothelium-derived relaxing factor, were investigated in a 6-h model of myocardial ischemia (MI) with reperfusion in open-chest, anesthetized cats. Acidified NaNO2 (12.5-50 mmol/kg/hr) was infused i.v., starting 30 min postocclusion followed by reperfusion 1 hr later, in cats subjected to MI by occlusion of the left anterior descending coronary artery. Acidified NaNO2 infusion (25 and 50 mmol/kg/hr) resulted in significantly lower plasma creatine kinase activities at every time beyond 1 hr for the MI + vehicle group, and was not significantly different when compared to sham MI + NaNO2 controls. The areas at risk expressed as percentage of the total left ventricular weights were not significantly different between the MI + vehicle and MI + acidified NaNO2 groups. However, the necrotic area expressed as a percentage of the myocardial area at risk was significantly lower in the 25 and 50 mmol/kg/hr NaNO2-treated cats. Cardiac myeloperoxidase activities indicated that significantly fewer neutrophils were attracted to the ischemic zone of the NaNO2-treated MI cats when compared to the vehicle-infused MI cats. Acidified NaNO2 significantly inhibited platelet aggregation in a dose-dependent manner in cat platelet-rich plasma. Thus, acidified NaNO2 exerts a significant protective action during ischemia and reperfusion injury, which suggests that endothelium-derived relaxing factor has a cardioprotective effect in MI.

Topics: Animals; Blood Pressure; Cats; Coronary Disease; Creatine Kinase; Heart; Heart Rate; Male; Myocardial Reperfusion Injury; Nitrites; Peroxidase; Platelet Aggregation; Platelet Aggregation Inhibitors; Sodium Nitrite

The effects of acidified sodium nitrite (NaNO2), a releaser of nitric oxide (NO), combined with human superoxide dismutase (hSOD), were investigated in a 6-hour model of myocardial ischemia (MI) with reperfusion in open-chest, anesthetized cats. Acidified NaNO2 (12.5 mmol/kg/hr) was infused intravenously in cats starting 0.5 hour after occlusion of the left anterior descending (LAD) coronary artery, which was reperfused 1.5 hour following occlusion. Significantly lower plasma creatine phosphokinase activities were observed at all times beyond 3 hours for MI cats given NaNO2 + hSOD when compared with the other MI groups. The areas-at-risk expressed as percentages of the total left ventricular weights were not significantly different among any of the MI groups. However, the necrotic area expressed as a percentage of the myocardial area-at-risk was significantly lower in the MI + NaNO2 + hSOD-treated cats compared with all other MI groups. The NaNO2-treated group also produced a significant decrease in the necrotic area relative to the area-at-risk. Cardiac myeloperoxidase (MPO) activities indicated no significant difference in number of neutrophils attracted to the ischemic zone in the NaNO2 + hSOD-treated MI cats when compared with the other MI groups. Acidified NaNO2 + hSOD together exert significant protection on the myocardium subjected to ischemia and reperfusion injury. NaNO2 may act synergistically with hSOD to prolong the action of NO by scavenging free radicals that inactivate NO.

Topics: Animals; Cats; Coronary Disease; Creatine Kinase; Drug Synergism; Drug Therapy, Combination; Male; Myocardial Reperfusion Injury; Myocardium; Nitrites; Peroxidase; Sodium Nitrite; Superoxide Dismutase

Changes in segmental forces of contraction (determined by a strain gauge arch) in non-ischemic (normal) and ischemic regions of the same left ventricular wall were studied in dogs anesthetized with morphine and pentobarbital. A branch of the left anterior descending coronary artery was completely occluded, and 10 min after occlusion coronary dilators were injected intravenously. The results can be summarized as follows. 1) Coronary occlusion markedly reduced the segmental force of contraction in the ischemic region, while it did not affect that in the normal region. Heart rate did not change markedly after coronary occlusion. 2) Either nitroglycerin (100 microgram/kg) or sodium nitrite (2.5 mg/kg) increased heart rate, and it also increased segmental force of contraction in the normal region while it decreased that in the ischemic region. 3) Papaverine (1 mg/kg) increased heart rate and segmental forces of contraction in both normal and ischemic regions. 4) Dipyridamole (250 microgram/kg) slightly increased heart rate, and it also increased segmental force of contraction in the normal region but not in the ischemic region.

Topics: Animals; Coronary Disease; Dipyridamole; Dogs; Female; Heart Rate; Heart Ventricles; Male; Myocardial Contraction; Nitroglycerin; Papaverine; Sodium Nitrite; Vasodilator Agents