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Biomedical subjects

E S Kirk

Publications and source records attributed to E S Kirk.

At least 37 records · Page 2Linked to original sources
PubMed1982

The effects of the coronary capacitance on the interpretation of diastolic pressure-flow relationships.

The effects of coronary capacitance on instantaneous pressure-flow (P/F) relationships were analyzed using a theoretical model of coronary flow during diastole that included capacitance. The magnitude of the discrepancy between actual intramural and instantaneously derived P/F relationships was predicted to be dependent on the ratio of two natural decay constants (central aortic decay constant/intrinsic coronary decay constant). The effects of coronary capacitance are eliminated using constant pressure conditions. The instantaneous (dynamic) and constant pressure (static) P/F relationships were compared experimentally using a reservoir to provide constant pressure perfusion during prolonged diastoles in heart blocked dogs. In the presence of coronary tone, zero flow pressure intercepts (Pzf) of 27.1 +/- 6.6 and 11.0 +/- 3.0 mm Hg were obtained under dynamic and constant pressure conditions respectively, P less than 0.001. After maximal vasodilation, Pzf of 14.2 +/- 4.5 mmHg and 10.7 +/- 2.4 mmHg were obtained under dynamic and constant pressure conditions, respectively, P = NS. Pzf derived under constant pressure conditions were independent of the state of coronary vasomotor tone with a value about 11 mmHg. The slopes of the dynamic P/F relationships tended to be greater than those derived from constant pressure conditions. This may suggest an additional component of increasing coronary resistance during diastole that could not be readily assessed under dynamic conditions. We conclude that coronary capacitive effects and resistance changes during diastole severely limit the interpretation of instantaneous dynamic P/F relationships. Diastolic coronary perfusion ceases at about 11 mm Hg and is independent of coronary tone when capacitive effects are eliminated.

Animals↗
PubMed1981

Beneficial effect of amrinone on myocardial oxygen consumption during acute left ventricular failure in dogs.

In 11 dogs ischemic left ventricular failure characterized by a 30 percent reduction in cardiac output and a left ventricular end-diastolic pressure of 18 mm Hg or more was produced by proximal occlusion of the left anterior descending coronary artery followed by serial occlusions of the distal left circumflex coronary artery. Administration of amrinone in an intravenous bolus injection followed by a constant infusion produced improvements in cardiac output (from 1.62 +/- 0.50 to 2.19 +/- 0.52 liters/min [mean +/- standard deviation], p less than 0.05), left ventricular end-diastolic pressure (from 21.6 +/- 3.5 to 11.0 +/- 5.4 mm Hg, p less than 0.05) and peak positive rate of rise of left ventricular pressure [dP/dt] (from 1,264 +/- 241 to 1,800 +/- 458 mm Hg.s-1, p less than 0.05). These improvements were maintained throughout the 20 minute period of therapy. No significant alteration in heart rate or arterial pressure was noted. In parallel with the hemodynamic improvement myocardial oxygen consumption improved to 0.094 +/- 0.05 and 0.092 +/- 0.04 vol.min-1.g-1 after 2 and 20 minutes, respectively, of amrinone compared with 0.124 +/- 0.05 during left ventricular failure (both p less than 0.05). The effects of amrinone on left ventricular failure are due to augmented contractility and mild systemic vasodilatation. The reduction in myocardial oxygen consumption during amrinone-treated left ventricular failure presumably results from a reduction in ventricular wall tension that more than offsets the effect of an increase in contractility.

Acute Disease↗
PubMed1981

The histological lateral border of acute canine myocardial infarction. A function of microcirculation.

Studies from this laboratory have shown that the border of a 24-hour canine infarct is histologically sharp and is composed of numerous interdigitating peninsulas of necrotic and normal tissue. To see if this sharp boundary is spatially related to the capillary beds of occluded and non-occluded arteries, the left anterior descending artery (LAD) was ligated in five mongrel dogs. Twenty-four hours later, white silicone rubber (Microfil) was injected into the LAD distal to the ligature; simultaneously and under the same pressure, red Microfil was injected into the left main coronary artery (LMCA). In hematoxylin and eosin sections from the border of the infarct, capillaries supplied by the LAD (white) were either in areas of necrosis, in normal epicardium or, rarely, in normal tissue along the lateral boundary; those supplied by the LMCA (red) were almost always in normal regions. Quantitative evaluation of this relationship revealed that the majority of the vessels in the normal and necrotic tissue were concordant (i.e., that normal tissue was supplied by the LMCA, and necrotic tissue by the LAD). However, a small zone of vascular discordance, averaging approximately 30 micrometers in width, was present along the infarct boundary, possibly representing a narrow border zone of little consequence. Hence, the complex interdigitation of normal and necrotic tissue in the lateral border of an infarct is predominantly a function of the interdigitation of the capillary beds supplied by the occluded and nonoccluded arteries.

Acute Disease↗
PubMed1980

Comparative effects of vasodilator drugs on large and small coronary resistance vessels in the dog.

One of the mechanisms whereby nitroglycerin is considered to reduce myocardial ischaemia and spasm is its preferential reduction of resistance of large compared with small coronary arteries. Accordingly, the action of nitroglycerin on these two resistance beds was compared with newer coronary vasodilator drugs. Following intracoronary administration of boluses of each drug, large and small vessel coronary resistance was measured in 14 dogs by recording the pressure drop across each vascular bed while flow was held constant. The dose of each drug was given to reduce small vessel resistance by 30% (range means 27 to 32%) which peaked at 5 to 10 s and declined to 8 to 18% at 1 min when reduction in large vessel resistance was at its maximum. At 1 min the large vessel resistance was decreased 56 +/- 5% by nitroglycerin, 23 +/- 5% by nitroprusside, 8 +/- 4% by perhexiline, 0 +/- 5% by verapamil and increased 8 +/- 5% by nifedipine. Nitroprusside reduced the large vessel resistance significantly less than nitroglycerin (P < 0.001) for an equivalent reduction in small vessel resistance. Perhexiline, verapamil and nifedipine did not significantly reduce large vessel resistance and the discrepancy between these results and their antianginal and antispasm effect in humans was not apparent from these experiments. However, a suitable model of coronary spasm in the dog following ergonovine injection could not be created.

Animals↗
PubMed1979

End-capillary loops in the heart: an explanation for discrete myocardial infarctions without border zones.

Separate perfusions of canine coronary arteries with colored silicone-rubber compound reveal that in the region where two microcirculations abut, capillaries derived from individual large vessels are discrete, with no interconnections. Terminal homologous capillaries from loops rather than anastomosing with heterologous capillaries. This anatomic arrangement may account for discrete myocardial infarctions without ischemic border zones.

Animals↗
PubMed1978

Mechanisms of beneficial effects of vasodilators and inotropic stimulation in the experimental failing ischemic heart.

Both vasodilator and inotropic agents improve cardiac function in ischemic heart failure. However, since vasodilators may reduce coronary perfusion pressure and inotropic interventions may increase myocardial oxygen consumption (MVO2), both may increase myocardial ischemia. Accordingly, we determined myocardial blood flow and MVO2 in a canine model of failure induced by propranolol and volume load combined with acute coronary ligation. Both nitroprusside and digitalis reduced ventricular diastolic pressure (LVDP) and increased myocardial blood flow in the ischemic subendocardium. Decreased systolic wall tension also caused a significant reduction MVO2. The benefit of nitroprusside in failing hearts was obtained even with the addition of critical obstruction of the main left coronary artery (LCA). The role of preload reduction is emphasized by the contrasting results with nitroprusside in hearts with low LVDP: (1) decreased myocardial blood flow in ischemic subendocardium, and (2) left ventricular decompensation in animals with critical LCA obstruction. Thus, reduction of LVDP, which decreases subendocardial ischemia, is essential for the beneficial effects of vasodilators and inotropic interventions in ischemic heart failure. Decreased MVO2 caused by reduced heart size may also have a salutary role.

Animals↗
PubMed1978

The histologic border zone of acute myocardial infarction--islands or peninsulas?

Observation of isolated islands of apparently surviving myocardium within areas of necrotic tissue at the edge of myocardial infarctions has been interpreted by some as histologic evidence of a unique "border zone" region. Serial section reconstruction of transmural canine myocardial infarctions was performed in this study to establish whether these islands were truly isolated or were continuous peninsulas of tissue separated by the plane of section. Three-dimensional analysis of the infarcts revealed no true islands but instead demonstrated a region composed of highly complex interdigitating peninsulas. We conclude that there is an extremely irregular but sharp boundary demarcating normal and infarcted myocardium with no intermediate zone. This observation is discussed in relation to recent data, based on coronary blood flow and creatine phosphokinase analysis, which also demonstrates a sharp boundary between the normal and infarct zones.

Animals↗
PubMed1977

The effect of mannitol following permanent coronary occlusion.

Quantitative comparisons of infarcts 24 hours after ligation of the left anterior descending coronary artery (LAD) via thoracotomy were made in 13 control and 13 dogs treated with i.v. 25% mannitol, 2 ml/min for 4 hours following occlusion. Mannitol increased serum osmolarity by 44+/-4 mOsm/L (mean +/- 1 SE) with hemodynamic effects limited to a small increase in left ventricular dP/dt. Nonperfusible tissue measured by planimetry at 24 hours was similar in both groups (46+/-4% of area defined with dye injected into the distal LAD for control versus 48+/-5% for mannitol treated dogs, P = NS). Creatine phosphokinase activity in infarcted tissues was also similar in both groups. Myocardial blood flows measured with radioactive microspheres were also similar in both groups. Collateral conductance calcultaed from retrograde flow and aortic pressure increased with the 24 hour period by 146+/-23% in the control dogs; in the mannitol treated dogs, collateral increased only 38+/-14% (P less than 0.001). Thus mannitol had no effect on ultimate infarct size. Moreover, mannitol appeared to hinder the development of collateral vessels.

Animals↗
PubMed1977

Absence of a lateral border zone of intermediate creatine phosphokinase depletion surrounding a central infarct 24 hours after acute coronary occlusion in the dog.

Myocardial creatine phosphokinase (CPK) activity was measured as an indicator of cell viability 24 hours after ligation of the left anterior sescending coronary artery (LAD) in normal myocardium, the entire region supplied by the LAD, and individual samples from the border and center of the infarct. Tissue supplied by the LAD and delineated by dye was carefully dissected from normal tissue along the stained border, CPK activity in the ischemic myocardium was calculated by assuming normal CPK activity in the ischemic myocardium was calculated by assuming normal CPK activity in normal myocardium interdigitating with ischemic tissue at the border. Normal tissue was marked prior to occlusion with microspheres injected into the left atrium, whereas the distal portion of the LAD was perfused separately with unlabeled blood from a reservoir. With this correction, the CPK activity in the ischemic tissue from the lateral border of the infarct was essentially the same as in samples from the center, whereas that in the normal tissue immediately adjacent to the stained border was equal to values in remote normal myocardium. Thus, CPK depletion throughout the entire ischemic myocardium was nearly equal to CPK depletion in the center of the infarct. The uncorrected intermediate CPK levels in the individual samples from the border of the stained region correlated with the amount of normal tissue contaminating these samples. However, differences in CPK depletion across the heart wall resulted in the most depletion in the subendocardium and the least in the epicardium. Further more, coronary collateral blood flow measured 10 minutes after occlusion correlated well with the subsequent extent of CPK depletion.

Animals↗
PubMed1976

Pulmonary angiotensin-converting enzyme. Interspecies homology and inhibition by heterologous antibody in vivo.

Goat antibody against pure rabbit pulmonary angiotensin-converting enzyme was used to probe homology of converting enzymes from other species. Immunologically cross-reactive material was found in detergent-solubilized extracts of lung particles from rat, guinea pig, and dog by double immunodiffusion, radioimmunoassay, and inhibition of enzyme activity. No homology was demonstrable with bovine, frog, or chicken lung extracts. Antibodies from different individual goats yielded comparable estimates of homology by immunodiffusion and radioimmunoassay. In contrast, they varied greatly in extent and specificity of their inhibitory action on heterologous enzyme activity. The vasopressor effect of angiotensin I and the vasodepressor effect of bradykinin were diminished and potentiated, respectively, in rats treated with anti-rabbit enzyme antibody. A smaller but significant immune-dependent inhibition of the vasopressor response to angiotensin II was also observed.

Angiotensin II↗
PubMed1976

Comparative effects of nitroglycerin and isosorbide dinitrate on coronary collateral vessels and ischemic myocardium in dogs.

To determine the effect of isosorbide dinitrate or ischemic myocardium, this agent was administered to dogs with well developed coronary collateral vessels 8 to 14 weeks after embolization and subsequent occlusion of the left anterior descending coronary artery. After thoracotomy the left coronary artery was cannulated and perfused with blood from the femoral artery. The distal left anterior descending artery was cannulated to monitor peripheral coronary pressure. Regional contractile force in the normal left circumflex and potentially ischemic left anterior descending regions was measured with isometric strain gauge arches sewn to the epicardium. Moderate decreases in coronary perfusion pressure averaging 27 mm Hg produced selective ischemia in the myocardium beyond the site of occlusion of the left anterior descending artery. Under these conditions the average increase in peripheral coronary pressure produced by intracoronary injection of isosorbide dinitrate was 9.0 mm Hg, whereas contractile force in the ischemic region increased by 30 percent. The contractile force was unchanged in the normal regions. Therefore, isosorbide dinitrate can dilate coronary collateral vessels and improve contractile force in ischemic areas. Intracoronary injection of nitroglycerin had similar effects. The durations of responses to isosorbide dinitrate and nitroglycerin were remarkably similar: 6.4 and 6.7 minutes, respectively. Although isosorbide dinitrate can directly dilate coronary collateral vessels, its effects are not longer lasting than those of nitroglycerin.

Animals↗
PubMed1976

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.

Adenosine↗
PubMed1976

Redistribution of collateral blood flow from necrotic to surviving myocardium following coronary occlusion in the dog.

Early changes in collateral blood flow after acute coronary occlusion may be critical for survival of ischemic myocardium. We used 15-mum radioactive microspheres to study myocardial blood flow in thoracotomized dogs 10 minutes and 24 hours after occlusion of the left anterior descending coronary artery (LAD). The ischemic area was delineated by dye injected into the distal artery, and indentification of potentially ischemic samples was confirmed by a newly developed technique in which microspheres were excluded from the normally perfused LAD. Layers were separated into necrotic or normal as defined by gross inspection and confirmed by histological examination and creatine phosphokinase assay. Infarction always involved endocardial layers and extended toward the epicardium. Average myocardial blood flow in 48 necrotic samples from 16 dogs either remained low (less than 0.05 ml/min g-1) or declined, falling from 0.11 +/-0.02(SE) at 10 minutes to 0.05 +/-0.01 ml/min g-1 at 24 hours (P less than 0.001). In contrast, in the 32 normal-appearing samples which were ischemic at 10 minutes, flow increased from 0.24 +/-0.03 to 0.39 +/-0.04 ml/min g-1 (P less than 0.001). Flow in control myocardium was 1.43 +/-0.12 and 1.04 +/-0.07 ml/min g-1, respectively. Peripheral mean coronary arterial pressure increased from 26 +/- 3 to 35 +/- 3 mm Hg, largely because of enlargement of collateral vessels; collateral conductance calculated from retrograde flow in 14 dogs increased from 0.023 +/- 0.005 after occlusion to 0.051 +/- 0.009 ml/min mm Hg-1 24 hours later (P less than 0.001). Thus, coronary collateral blood flow is redistributed from necrotic endocardial layers to surviving epicardial ones. In combination with a developing collateral supply this process may be essential for sparing myocardium after coronary occlusion.

Animals↗
PubMed1975

Inhibition of coronary blood flow by a vascular waterfall mechanism.

The mechanism whereby systole inhibits coronary blood flow was examined. A branch of the left coronary artery was maximally dilated with an adenosine infusion, and the pressure-flow relationship was obtained for beating and arrested states. The pressure-flow curve for the arrested state was shifted toward higher pressures and in the range of pressures above peak ventricular pressure was linear and parallel to that for the arrested state. Below this range the curve for the beating state converged toward that for the arrested state and was convex to the pressure axis. These results were compared with a model of the coronary vasculature that consisted of numerous parallel channels, each responding to local intramyocardial pressure by forming vascular waterfalls. When intramyocardial pressure in the model was assigned values from zero at the epicardium to peak ventricular pressure at the endocardium, pressure-flow curves similar to the experimental ones resulted. Thus, we conclude that systole inhibits coronary perfusion by the formation of vascular waterfalls and that the intramyocardial pressures responsible for this inhibition do not significantly exceed peak ventricular pressure.

Adenosine↗