Coronary Occlusion In Dogs Research Articles

Loss of regional ventricular postextrasystolic potentiation after coronary occlusion in dogs.

Postextrasystolic potentiation following coronary artery occlusion was studied serially using pairs of ultrasonic crystals to measure regional myocardial function in control, marginally ischemic, and ischemic segments of the left ventricle in dogs. Prior to coronary occlusion (CO), percent shortening in control (normal) segments increased by an average of 51.4 +/- 4.6% in the beat after a premature ventricular contraction (post-PVC beat), and this response changed little after coronary occlusion. During the 1st min after CO, in ischemic segments, systolic expansion developed but was replaced by active shortening in post-PVC beats; however, after 3 min of CO (average) and thereafter, there was no net positive shortening in post-PVC beats. In marginally ischemic segments early after CO, hypokinesia developed, but there was marked augmentation of percent shortening (208.6 +/- 32.6%) which persisted in post-PVC beats even after 2 h. It is concluded that loss of postextrasystolic potentiation occurs rapidly in ischemic regions after CO and is not indicative of irreversible damage; partially ischemic regions retain this mechanism for prolonged periods.

Irreversible myocardial damage resembling catecholamine necrosis secondary to acute coronary occlusion in dogs: Its prevention by propranolol

Coagulative myocytolysis resembling catecholamine myocardial necrosis is demonstrated in ischemic and normal cardiac muscle in dogs dying of ventricular fibrillation following acute ligation of the circumflex branch of the left coronary artery. The frequency of this lesion, possibly due to secondary sympathetic overstimulation, is significantly reduced by pre-treatment with propranolol.

Differentiation of transiently ischemic from infarcted myocardium by serial imaging after a single dose of thallium-201.

Myocardial 201Tl uptake and regional blood flow by the microsphere technique were determined in anesthetized dogs undergoing either 20 min of coronary occlusion and 100 min of reperfusion (N = 10) or 120 min of occlusion (N = 4). In both groups, 201Tl was injected intravenously after 10 min of occlusion. In transiently occluded dogs, regional flow at the time of 201Tl administration was reduced to 8 +/- 3% of normal flow in endocardial layers of the central ischemic zone. After 100 min of reperfusion, flow values were not significantly different from normal. 201Tl activity after reperfusion rose to 56 +/- 5% of normal, demonstrating that redistribution of the radionuclide occurred during the reflow period. In animals with persistent occlusion, there was a significant relationship between 201Tl uptake and flow (r = 0.95) and no evidence of redistribution of 201Tl during the two hour occlusion period. In another five dogs receiving 201Tl, serial gamma camera images obtained during reperfusion showed increasing uptake of the tracer in apical defects which returned to normal by 4 hours of reflow. Thirteen patients with stable angina received 2 mCi of 201Tl intravenously at peak exercise, and multiple gamma camera images obtained serially. All demonstrated zones of diminished 201Tl uptake 10 min after exercise. Defects which partially or completely disappeared within 1-6 hours postexercise corresponded to areas supplied by coronary arteries with significant stenoses. Persistent defects were present in regions of old myocardial infarction. Six additional patients with acute myocardial infarction demonstrated 201Tl myocardial defects which showed no significant change over 6 hours. Thus, redistribution of 201Tl into ischemic myocardium was demonstrated during transient coronary occlusion in dogs and after exercise stress in man. Sequential imaging after a single dose of 201Tl at the time of exercise may provide a means for distinguishing between transient perfusion abnormalities or ischemia and myocardial infarction of scar.

Effect of drugs on conduction delay and incidence of ventricular arrhythmias induced by acute coronary occlusion in dogs

The effects of various drugs on delayed activation of the ischemic myocardium and the incidence of ventricular arrhythmias were studied in 34 open-chest anesthetized dogs. The left anterior descending coronary artery was occluded for 6 minutes before and 42 minutes after administration of aprindine (2.85 mg/kg body weight), quinidine (8 mg/kg) and verapamil (0.2 mg/kg) and during infusion of isoproterenol (0.2 microng/min). The time intervals from the onset of the QRS complex to the major deflection of the bipolar electrograms recorded within the normal and ischemic zones were measured at cycle lengths of 500, 400 and 300 msec and were correlated with the development of ventricular arrhythmias. At a cycle length of 500 msec, aprindine increased by 19.5 msec the delay in activation time produced by coronary ligation alone (P less than 0.05), whereas verapamil reduced by 10 msec the extent of ischemia-induced conduction delay (P less than 0.05). The delay in activation time in the ischemic zone was not significantly altered by quinidine or isoproterenol. The incidence of ventricular arrhythmias was increased by aprindine (from 1 in 11 to 8 in 11 dogs), decresed by verapamil (from 3 in 7 to 0 in 7 dogs) and was not changes by quinidine or isoproterenol. Thus, delayed activation of the ischemic myocardium appears to play an important role in the genesis of early arrhythmias due to myocardial ischemia, and drugs that significantly depress conduction in the ischemic myocardium may predispose to the development of ventricular arrhythmia whereas those that improve conduction may be protective. Contrary to their effects on slow channel-dependent conduction, verapamil improved and isoproterenol worsened conduction during ischaemia.

Distribution of coronary blood flow during acute coronary occlusion in dogs. Effect of nicotinic acid and sodium salicylate

The effects of the antilipolytic agents nicotinic acid (NA) and sodium salicylate (SS) on the distribution of coronary blood flow during acute myocardial ischaemia were studied in open chest dogs. Fifteen min following experimental coronary artery occlusion, blood flow in the ischaemic myocardium was on average 28% of flow in the non-ischaemic myocardium. The reduction in blood flow in the ischaemic mycardium was more pronounced in the endocardial than in epicardial halves of the myocardium. No significant change in blood flow was observed after administration of NA or SS in either the ischemic or nonischemic part of the myocardium. Both drugs reduced the extent of myocardial ischaemic injury as shown by reduced epicardial ST-segment elevations. Arterial concentrations of fatty acids were lowered by NA or SS, whereas the mechanical activity of the heart remained unchanged. It is concluded that the reduction of acute myocardial ischaemic injury effected by NA or SS is not due to changes in myocardial blood flow, but more likely to lower myocardial oxygen demand related to reduced fatty acid utilization.

Coronary steal: Its role in detrimental effect of isoproterenol after acute coronary occlusion in dogs

Using epicardial electrograms others have established that infusion of isoproterenol increases myocardial injury after acute coronary occlusion. To define the contribution of alterations in collateral blood flow to this increased ischemia, isoproterenol was administered to 10 dogs. After pretreatment with practolol in doses that successfully block inotropic but not vascular effects of beta adrenergic stimulants, intracoronary isoproterenol continued to enhance the magnitude of S-T segment elevation in ischemic areas. Thus, vasodilation induced by isoproterenol appears to divert flow from the ischemic area. To test this hypothesis, intracoronary adenosine was given to cause coronary vasodilation without enhancing inotropy. S-T segment elevation at ischemic and adjacent sites was significantly increased. Neither agent had systemic effects, but each increased coronary blood flow while concomitantly decreasing collateral flow as evidenced by a reduction in retrograde coronary flow and peripheral coronary pressure. In addition, adenosine significantly diminished the rate of xenon-133 clearance from the ischemic myocardium. Thus, isoproterenol, in addition to its positive inotropic effect, increases myocardial injury by its vascular action. Collateral blood flow to acutely ischemic myocardium is diminished by the production of a coronary steal. Intravenously administered isoproterenol additionally diminishes collateral flow by decreasing coronary perfusion pressure. It is postulated that any agent that causes either a primary or secondary coronary vasodilation may cause a coronary steal and subsequently enhance myocardial injury.

Effects of verapamil on regional myocardial blood flow and [formula omitted] segment. Role of the induced bradycardia

The effects of verapamil on regional myocardial blood flow and on the ST segment were studied in both normal and ischemic regions in dogs with and without cardiac pacing. In the absence of cardiac pacing, verapamil (0.05 mg/kg/min/10 min) induced marked bradycardia, a drop in blood pressure and an increase in epicardial and endocardial flows both in normal and ischemic regions of the heart. However, in ischemic regions, redistribution was favorable since the endo/epi ratio increased from 0.46 to 0.61 ( p<0.01) whereas this ratio did not vary in normal regions (0.94 vs. 0.92). This increase is accompanied by less marked ST segment elevation during coronary occlusion in dogs treated with verapamil. In dogs with cardiac pacing, administration of verapamil under the same conditions again induced a drop in blood pressure and, in normal regions only, a homogeneous but less marked increase in epicardial and endocardial flows, the endo/epi ratio varying from 0.94 to 0.98. In contrast, in ischemic regions, blood flow was not modified by verapamil, but the endo/epi ratio dropped from 0.46 to 0.31 ( p<0.01), while the ST segment elevation observed did not differ from that recorded during the control occlusion. These results demonstrate the major role of verapamil-induced bradycardia in the anti-anginal effects of this drug.

Relationship of epicardial ST segment elevation to the plasma free fatty acid/albumin ratio during coronary occlusion in dogs.

1. Intravenous infusions of lipid-free albumin were used to lower the arterial non-esterified fatty acids (NEFA)/albumin ratio during coronary occlusion in dogs. 2. Reduction of the NEFA/albumin ratio was accompanied by proportionate reductions in myocardical uptake of NEFA and the degree of ST segment elevation in epicardial electrocardiographic recordings from the ischaemic zone. Aortic pressure and heart rate were unchanged. 3. Infusions of control albumin preparations had no effect on the NEFA/albumin ratio or ST segment elevation. 4. These observations support the proposition that the disturbance of cellular function during myocardial ischaemia is influenced by the degree of saturation of albumin-binding sites with NEFA and by their availability.

Effects of dichloroacetate on myocardial substrate extraction, epicardial ST-segment elevation, and ventricular blood flow following coronary occlusion in dogs.

Glucose metabolism in the healthy heart is stimulated by dichloroacetate (DCA). The possibility has been examined in dogs that DCA, by increasing glucose utilization, might limit the severity of acute myocardial ischaemic injury. Intravenous administration of DCA reduced the degree of epicardial ST-segment elevation induced by subsequent coronary occlusion, both under basal conditions and during isoprenaline infusion. A similar result was obtained when DCA was given during an established coronary occlusion. This effect could not be explained by changes in mean aortic blood pressure, heart rate, or regional myocardial blood flow as measured by radioactive microspheres. Measurements in arterial and coronary sinus blood demonstrated an increase in the extraction of glucose and a decrease in that of FFA by the heart. Glucose extraction also tended to be increased in the ischaemic zone, as shown by the differences in the concentrations of these substrates between arterial blood and blood obtained from the local vein draining that zone. Lactate release by the ischaemic zone was markedly reduced.

Effects of p-chlorophenoxyisobutyrate on myocardial free fatty acid extraction, ventricular blood flow, and epicardial ST-segment elevation during coronary occlusion in dogs.

The effect of p-chlorophenoxyisobutyrate (CPIB) on ST-segment elevation in epicardial electrocardiographic recordings was studied during coronary artery occlusion in dogs. Occlusion alone raised the sum of ST-segment elevations (sigmaST) to 26 +/- 6 mV (mean +/- SEM). Intravenous (i.v.) administration of CPIB 30 min before re-occlusion reduced sigmaST to 14 +/- 3 mV (P less than 0.03). A continuous i.v. infusion of isoproterenol increased sigmaST to 74 +/- 11 mV. Pretreatment with CPIB reduced sigmaST during isoproterenol infusion to 40 +/- 7 mV (P less than 0.005). CPIB had no effect on mean aortic blood pressure, heart rate, or regional myocardial blood flow, as measured by radioactive microspheres. Arterial free fatty acid (FFA) concentrations were reduced by CPIB from 466 +/- 41 to 221 +/- 44 muEq/L (P less than 0.001) in the basal state, and from 1966 +/- 183 to 1429 +/- 209 muEq/L (P less than 0.001) during isoproterenol infusion. The reduction in arterial FFA concentration was associated with a proportionate decrease in the myocardial extraction of FFA. Similar changes were observed when CPIB was administered during an occlusion which had been established 10 min earlier. These observations support other evidence that the severity of acute myocardial ischemic injury in dogs is positively correlated with the myocardial extraction of FFA, and that the severity of the ischemic injury can be reduced by effective antilipolytic therapy.

On the nature of protection by propranolol against myocardial necrosis after temporary coronary occlusion in dogs

Propranolol has been shown to reduce the extent of necrosis that develops after temporary coronary occlusion in dogs. To determine whether this protective action was related to beta adrenergic blockade or to direct effects, necrosis was quantitated in the posterior papillary muscle 2 to 4 days after 40 minute periods of coronary occlusion in anesthetized open chest dogs. Groups of dogs either were untreated or were pretreated with doses of d,l-propranolol, 0.005 to 5 mg/kg body weight, or doses of d-propranolol 2.5 or 5 mg/kg. Necrosis was greatly reduced in dogs treated with 5 mg/kg of d,l-propranolol. This protective effect was significant but quantitatively less with 0.5 and 0.05 mg/kg of d,l-propranolol. A dose of 0.005 mg/kg d,l-propranolol and d-propranolol failed to alter myocardial necrosis significantly. The dose-related reduction of necrosis with d,l-propranolol correlated with a similar dose relation for beta adrenergic blockade and suggested that a protective effect was related to beta blockade. The reduction of necrosis with 0.05 and 0.5 mg/kg of d,l-propranolol (a level at which direct “membrane stabilizing” effects are insignificant) suggested that direct effects were not essential for protection. The negative results with d-propranolol further support our conclusion that propranolol reduces myocardial ischemic injury through beta adrenergic blockade rather than through direct myocardial actions.

Histochemical studies of monoamine oxidase in experimental myocardial infarctions.

Sequential histochemical studies were conducted to determine the level of monoamine oxidase (MAO) activity in the infarcted tissue of the experimental myocardial infarction in dog. MAO activity was not found in the normal heart muscle, but the activities were present in the wall of the coronary artery histochemically. Fibroblasts and collagen fibers began to take the place of the destroyed heart muscles in the infarcted area from 10 days after the coronary occlusion in dogs, and MAO activities were noted sporadically in the fibroblasts and the interstices of the collagen fibers in the infarcted area. MAO activities increased histochemically in the fibroblasts and the fiber interstices in the infarcted area 10 days or more after the coronary occlusion. These findings suggested the presence of the active collagen metabolism outside the myocardial cells in the infarcted area in the recovery stage of the experimental myocardial infarction. It was also suggested that the interstices of the collagen fibers in the myocardial wall constituted the lymphatic ducts outside the blood vessels and that the MAO activity in serum determined by the method in which tryptamine hydrochloride was used as substrate might indicate the grade of fibrosis of the myocardial tissue in the infarcted areas.

Subendocardial S-T Segment Changes During Acute Coronary Occlusion

Subendocardial ischemia during coronary occlusion in dogs was studied using S-T segment elevations in unipolar subendocardial electrodes. Alterations in heart rate or cardiac output caused quantitatively similar changes in subendocardial and epicardial S-T elevation. Increasing blood pressure from 75 to 100 or 75 to 125 mm Hg caused a smaller reduction in subendocardial than in epicardial S-T elevation ( p < 0.01). In this situation, therefore, subendocardial ischemia tends to be maintained while epicardial ischemia is reduced by higher arterial pressures. Hemodynamic manipulations can cause quantitatively different changes in subendocardial and epicardial S-T segment elevation.

Effects of nitroglycerin and nitroglycerin-methoxamine during acute myocardial ischemia in dogs with pre-existing multivessel coronary occlusive disease.

Nitroglycerin (TNG) reduces ischemic injury during acute coronary occlusion in dogs with otherwise normal coronary arteries, but its effect in the presence of pre-existing multivessel coronary disease is unknown. We therefore examined the influence of TNG on acute ischemia in dogs with chronic multivessel coronary occlusions. The left anterior descending (LAD) coronary artery was acutely occluded by a balloon cuff in conscious dogs two weeks after placement of ameroid constrictors to produce gradual occlusion of the obtuse marginal and posterior descending coronary arteries. Adequacy of balloon and ameroid coronary occlusion and degree of collateralization were assessed by coronary angiography. Nitroglycerin decreased arterial pressure and increased heart rate. Myocardial ischemia, determined after LAD occlusion by summing ST-segment elevation (sigmaST) from eight intramyocardial electrodes, lessened with TNG in those six dogs whose heart rate increased less than 50 per cent, but increased in those four whose heart rate increased greater than 50 per cent. When TNG-induced change in either heart rate or arterial pressure was prevented by adding methoxamine, sigma ST was diminished even more (avg decrease 25 per cent; P smaller than 0.05). We conclude that, in the presence of pre-existing multivessel coronary occlusions, 1) TNG reduces ischemic injury during experimental acute coronary occlusion provided arterial pressure and heart rate responses are not excessive and 2) uniform improvement occurs when pressure and rate responses are abolished by an alpha-adrenergic agonist. Although results in animal studies must be extrapolated to the clinical situation with caution, these findings suggest that a similar pharmacologic approach might be applicable to the treatment of acute myocardial infarction in man, even in the presence of multivessel disease.

Nitroglycerin-induced reduction in the incidence of spontaneous ventricular fibrillation during coronary occlusion in dogs

Previous investigations have demonstrated that nitroglycerin reduces ischemic injury and enhances ventricular electrical stability during coronary occlusion in dogs. These beneficial effects were potentiated by preventing drug-induced hypotension with alpha adrenergic agonists. To determine whether nltroglycerin can prevent spontaneous post-occlusion ventricular fibrillation, 27 open chest dogs were assigned in random fashion to two groups—control (saline infusion) and nitroglycerin-treated (0.45 mg intravenous bolus infusion followed by 0.3 mg/ min continuous infusion). After 10 minutes of infusion the left anterior descending and septal coronary arteries were occluded at their origins. Hypotensive effects of nitroglycerin were prevented by intermittent intravenous doses of methoxamine; mean arterial pressure and heart rate in control and treated animals were thus indistinguishable. Infusions continued until ventricular fibrillation occurred or 30 minutes elapsed. Twelve of 13 control dogs died with ventricular fibrillation; only 7 of 14 nitroglycerin-treated dogs died ( P < 0.05). Thus, nitroglycerin may be capable of exerting important and unique beneficial effects in patients with acute myocardial infarction since, with its hypotensive effects obviated by alpha adrenergic agonists, it markedly diminishes ischemic injury, enhances ventricular electrical stability, and significantly reduces the incidence of spontaneous ventricular fibrillation in an experimental model of acute myocardial infarction.

The effect of digitalis on sinoatrial conduction in man

The effect of digitalis on sinoatrial conduction in man

Beneficial effects of lidocaine on incidence of ventricular fibrillation during coronary occlusion in dogs

Beneficial effects of lidocaine on incidence of ventricular fibrillation during coronary occlusion in dogs

Pulmonary function following acute coronary occlusion in dogs.

SummaryThe immediate cardiopulmonary effects following acute induced coronary occlusion are hyperpnea, systemic hypotension, and hyperventilation. The onset of hyperpnea and systemic hypotension is quite rapid. Arterial blood gas tensions reveal arterial hyperoxemia and hypocapnia, which may be partly due to hyperventilation. Arterial hypoxemia, following myocardial infarction, is a later event and possibly related to the pulmonary complications following myocardial infarction.

The influence of adrenaline secretion on the enzymes in heart muscle after acute coronary occlusion in dogs.

The influence of catecholamine secretion in the early stages of myocardial infarction upon the degree of myocardial lesions was investigated in dogs. It has been found that adrenaline release into the blood after the ligation of the coronary artery aggravates histoenzymatic changes in ventricular myocardium, manifested by the decrease in lactic and succinic dehydrogenases activity.

Cardiac rhythm disturbances and the release of catecholamines after acute coronary occlusion in dogs.

Acute occlusion of the anterior descending branch of the left coronary artery in dogs led to a development of ventricular arrhythmias in 39 of 68 animals examined. In 35 of these 39 dogs ventricular arrhythmias were associated with an increased release of catecholamines into the bloodstream. In dogs which failed to secrete catecholamines and showed no ectopic activity after coronary ligation, intravenous infusions of adrenaline provoked ventricular arrhythmias after coronary ligation, but not before. The specific β-receptor blocking agents, propranolol and I.C.I. 50 172, suppressed arrhythmias after coronary occlusion.