Ischemic Canine Myocardium Research Articles

Experimental myocardial infarction. XVI. The detection of inotropic contractile reserve with postextrasystolic potentiation in acutely ischemic canine myocardium

Postextrasystolic potentiation after a single closely coupled extrasystole may identify residual ventricular contractile performance in acutely ischemic myocardium without producing sustained secondary ischemic depression of myocardial function. Postextrasystolic potentiation was systematically used in eight open chest dogs to assess the progression of regional contraction abnormalities during a 10 minute occlusion of the left anterior descending coronary artery. Segment function was determined from pressure-length loop areas inscribed during right ventricular pacing at 128 ± 3 (mean ± standard error of the mean) beats/min, and after single closely coupled (179 ± 3 msec) extrasystoles. Despite a 50 percent decrease in border zone segment function, Postextrasystolic potentiation consistently augmented mechanical performance to control levels throughout the ischemic period. Central ischemic zone segment function deteriorated more profoundly, with the development of holosystolic aneurysmal bulging within 30 seconds after occlusion. Nonetheless, postextrasystollc potentiation produced marked inotropic augmentation, but not to control levels, for up to 10 minutes of ischemia. These results suggest that latent viability and contractile reserve may exist during brief periods of coronary occlusion.

Biochemical characteristics of mitochondrial populations and subpopulations isolated from ischemic canine myocardium

Biochemical characteristics of mitochondrial populations and subpopulations isolated from ischemic canine myocardium

Imaging of the inflammatory response in ischemic canine myocardium with 111indium-labeled leukocytes

Myocardial leukocyte infiltration is one hallmark of acute myocardial infarction. In order to detect noninvasively this inflammatory response associated with acute myocardial infarction, we produced coronary occlusion in eight dogs, intravenously administered autologously labeled indium-111 ( 111In) leukocytes and scintigraphically monitored accumulation of radionuclide in myocardium. Seventy-two hours after coronary occlusion, 111In-labeled white cells accumulated in regions corresponding to myocardial infarcts, and positive images with 111In-labeled leukocytes correlated well with images obtained with technetium-99m pyrophosphate and computer-reconstructed tomograms obtained with nitrogen-13-labeled ammonia. In contrast, two control dogs subjected to sham operation did not exhibit positive 111In-leukocyte images. Scintigraphic results with 111In-labeled leukocytes were verified in vitro by analysis of radioactivity in normal myocardium and in infarcts. Thus, leukocytic infiltration associated with acute myocardial infarction can be detected noninvasively in vivo.

Comparative Hemodynamic Effects of Coronary Vasodilators and Contrast Material on the Normal and Ischemic Canine Myocardium: Determination of the Optimal Agent for Clinical Augmentation of Coronary Blood Flow

The systemic hemodynamic and myocardial effects of potent vasodilators administered directly into the left coronary artery were determined and compared with the actions of contrast material in 10 anesthetized dogs in the normal state and in the presence of segmental myocardial ischemia. Contrast material (Renografin 76) caused systemic hypotension, rise in left ventricular diastolic pressure and decreases in LV dp/dt and dp/dt/LVP in both states. Doses of ATP (7.2 microgram/kg and 20 microgram/kg/min) which are maximally effective in augmenting coronary blood flow caused only mild arterial hypotension and minimal inotropic effects in both states. Nitroglycerin (3 microgram/kg and 10 microgram/kg/min) induced no inotropic effects but slightly greater arterial hypotension than ATP in both states. On the other hand, papaverine HCl (300 microgram/kg and 800 microgram/kg/min) induced profound increases in LV dp/dt and dp/dt/LVP, decreases in LVEDP and arterial hypotension in the non-ischemic state. In the presence of segmental ischemia, papaverine HCl caused significantly less increases in LV dp/dt and dp/dt/LVP, paradoxical increases in LVEDP in 5 dogs and ventricular fibrillation in 3 dogs. Thus, maximally effective vasodilatory doses of ATP causes only small alterations in hemodynamics and myocardial contractile state of the normal and ischemic heart. Similar doses of papaverine induce profound positive inotropic effects which are apparently deleterious to the ischemic heart.

Differences in the Velocity-Displacement Relationship of Systolic Contraction of Normal and Ischemic Canine Myocardium

In the canine model there exist major differences in the velocity-displacement relationships of systolic contraction between normal and ischemic myocardium. These differences are noninvasively measurable in vivo from video recordings of the fluoroscopic image of the heart, and can be detected within the time period of one cardiac cycle. Velocity data is plotted against the corresponding wall displacement on orthogonal axes (phase-space), producing characteristic loops which give an immediate visual indication of myocardial dysfunction.

Effects of perhexiline maleate on coronary flow distribution in the ischemic canine myocardium.

Intravenous perhexiline maleate in a canine preparation with fixed coronary flow increases coronary diastolic pressure. It also redistributes coronary flow so as to preserve endocardial flow. Myocardial oxygen consumption was reduced and lactate uptake enhanced by the drug. It had no effect upon the threshold for ischemic-induced left ventricular failure.

Monitoring of midmyocardial and subendocardial pH in normal and ischemic ventricles

Midmyocardial and subendocardial pH monitoring was used as an indirect method for continuous evaluation of regional canine myocardial ischemia. Left ventricular midmyocardial pH (pHm) at 4 mm. depth was monitored in 10 dogs, under resting conditions, by means of a 5 mm. Beckman pH probe. pHm was 6.96 +/- 0.03, recorded at myocardial temperatures of 35 to 37 degrees C. Ischemia was then produced by snare occlusion of the proximal left main coronary artery for 2 minutes. pHm decreased to 6.87 +/- 0.03 (p less than 0.01) at 1 minute and 6.80 +/- 0.04 (p less than 0.005) in 2 minutes. When flow was restored, pHm returned toward normal within 2 minutes (pH 6.86 +/- 0.03) and at 5 minutes had returned to control values (pH 6.93 +/- 0.03). In another 5 dogs under similar conditions, pHm at 4 mm. and subendocardial pH (pHe at 8 mm.) were measured. Baseline pHm (6.97 +/- 0.01) and pHe (6.84 +/- 0.02) levels were significantly different (p less than 0.0005). After 2 minutes of ischemia, pHm was 6.82 +/- 0.03, whereas pHe decreased to 6.78 +/- 0.04 (p less than 0.1). Five minutes after snare release, pHe remained at 6.73 +/- 0.07; pHm (6.93 +/- 0.03) returned to control values. Both pHm (6.93 +/- 0.02) and pHe (6.84 +/- 0.09) levels were normal 15 minutes after release of the snare. The midmyocardium and subendocardium have different pH levels which can be monitored. Ischemia produces different pH patterns in these layers. pHm returns to control values within 5 minutes after 2 minutes of ischemia, whereas pHe remains depressed for at least 5 minutes. pH monitoring provides an accurate and simple method for on-line evaluation of endocardial ischemia.

Effects of procainamide on the dispersion of recovery of excitability during coronary occlusion.

In 14 mongrel dogs, refractory periods were determined in nonischemic and acutely ischemic zones of myocardium during control conditions, 15 minutes after coronary ligation, and 10 and 20 minutes after a procainamide infusion. Following coronary ligation, refractory periods in the nonischemic area remained unchanged (100.8% of control) while in the ischemia area they decreased to 88.6% of control (P less than 0.02) causing a dispersion of refractoriness of 12.2%. After the administration of procainamide, refractory periods lengthened in the nonischemic as well as in the ischemic areas but the changes were such that the temporal dispersion caused by the coronary ligation was reduced from 12.2% to 5.5% (P less than 0.01) after 10 minutes, and to 5.0% (P less than 0.02) after 20 minutes of drug infusion. It is concluded that procainamide exerts different overall effects on the nonischemic and acutely ischemic canine myocardium. It is postulated that this action may play a role in the suppression of re-entrant arrhythmias.

Effects of lidocaine, phenytoin and quinidine on the ischemic canine myocardium

The effects of therapeutic concentrations of lidocaine, quinidine and phenytoin on the electrograms and excitability of ischemic canine myocardium were investigated. The threshold stimulation current was determined as the minimum current necessary to drive the ventricles at 300 msec intervals. Administration of the drugs did not change the threshold stimulation current of the control myocardium, but lidocaine (P less than 0.002), quinidine (P less than 0.01) and phenytoin (P less than 0.05) all markedly increased the threshold stimulation current of the ischemic tissue. The effects on the electrograms were small but consistent with current electrophysiological knowledge. This selective depression of the electrical activity of the ischemic tissue may form an important mechanism of action of these antiarrhythmic agents. However, this same effect may under certain conditions precipitate serious arrhythmias.

Effect of dipyridamole on the glycogen metabolism in the normal and ischemic canine myocardium.

Pretreatemtn of the dog with dipyridamole tended to increase the rate of acceleration of anaerobic metabolism in the myocardium induced by ligation of a small branch of the coronary artery.

Transmural gradient of retrograde collateral blood flow in acutely ischemic canine myocardium.

The contribution of retrograde coronary flow to total collateral flow was examined transmurally in anesthetized, open-chest dogs subjected to acute obstruction of the left anterior descending coronary artery. Regional coronary flow in normal and ischemic tissue was reflected by the tissue content of radioisotopes of potassium and rubidium and by radioactive microspheres. To measure total collateral flow, one isotope was administered when the retrograde cannula was clamped. The other isotope was administered when the cannula was opened to divert retrograde coronary flow away from acutely ischemic myocardium. Significant quantities of this isotope reached the ischemic region despite diversion of retrograde flow at an average rate of 3.5 ml/min. These results confirm earlier, but disputed, reports that total coronary collateral flow exceeds retrograde flow and are indicative of collateral pathways associated more closely with the microcirculation than with the larger epicardial arteries. Furthermore, the transmural distribution of myocardial blood flow in the ischemic tissue was altered nonuniformly by diversion of retrograde flow: 42 K or 86 Rb uptake was reduced to 25% of control in subepicardial tissue but only to 70% of control in subendocardial tissue. The transmural distribution of radioactive microspheres was similarly affected by diversion of retrograde flow. The results suggest that collateral pathways differ transmurally and may include significant luminal connections. Retrograde coronary flow is not a sensitive index of collateral flow to acutely ischemic subendocardial tissue.

Drug-induced changes in blood flow in the acutley ischaemic canine myocardium;relationship to subendocardial driving pressure.

SUMMARY 1. The effects of various drugs have been studied on blood flow and oxygen handling (availability, extraction and consumption) in both normal and acutely ischaemic regions of the canine myocardium. Ischaemia was produced by the acute ligation of the anterior descending branch of the left coronary artery. 2. Lidoflazine, like other coronary vasodilator drugs, increases blood flow in the normal myocardium, but does not increase flow through the ischaemic region. Drugs of this type may, in addition, open up ‘shunt’ vessels within the ischaemic region. 3. Of three cardiac stimulants studied, only oxyfedrine consistently increases blood flow through the ischaemic region; isoprenaline and glucagon do not. 4. Noradrenaline causes marked increases in flow through the ischaemic region: its effect is associated with an increase in coronary pressure in the artery distal to the ligature. 5. Evidence is put forward that the critical factor determining flow through ischaemic regions of the myocardium is the transventricular driving pressure. When the effects of various drugs on flow and driving pressure are analysed and compared, the only drugs that increase flow in an ischaemic region are those that increase the pressure gradient across the wall of the left ventricle.

Effects of carbochromen and dipyridamole on blood flow and heat production in the normal and ischaemic canine myocardium.

The coronary vasodilator drugs carbochromen and dipyridamole were capable of increasing local myocardial blood flow and decreasing myocardial metabolic heat production both in the normal canine myocardium and in the myocardium rendered ischaemic by acute ligation of a coronary artery. This is taken as further evidence for the existence of an active myocardial vasoconstrictor reflex, triggered off by coronary ligation.

Effect of nitroglycerin on total and regional coronary blood flow in the normal and ischaemic canine myocardium.

The effect of nitroglycerin on total coronary flow and its regional distribution was determined in normal conditions and in myocardial ischaemia. In normal hearts, capillary flow was 9·5% higher in the inner than in the outer myocardial half. When partial occlusion of coronary arteries was followed by infusion of noradrenaline, subendocardial flow was less than capillary flow in subepicardial layers. In these conditions, the administration of nitroglycerin resulted in a redistribution of capillary flow towards normal.