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Biomedical subjects

R B Jennings

Publications and source records attributed to R B Jennings.

At least 127 records · Page 7Linked to original sources
PubMed1976

Distribution of coronary collateral flow in acute myocardial ischaemic injury: effect of propranolol.

The local distribution of coronary collateral flow was mapped using 8 mu tracer microspheres following circumflex coronary occlusions in dogs. Overall flow to the ischaemic posterior papillary muscle and subjacent myocardium decreased to 21% of anterior free wall flow. Collateral flow was non-uniform, however, and was lower in the subendocardium (14%) than in the subepicardium (27%). Brief temporary occlusions with and without propranolol therapy showed that collateral flow was less and the inner/outer wall ratio was unaltered in treated animals. Although propranolol reduces infarct size after coronary occlusions, this effect appears not to be related to increases in collateral flow.

Acute Disease↗
PubMed1976

Cell volume regulation in acute myocardial ischemic injury.

Thin freehand slices of left ventricular papillary muscle of the dog, exhibit good cell volume regulation when incubated at 37 degrees for 60 minutes in oxygenated Krebs Ringer phosphate solution. The fine structure of the cells is maintained throughout the incubation. This in vitro system was developed in order to test the capacity of myocardial cells irreversibly injured by 60 minutes of ischemia to maintain cell volume. The results showed that irreversibly damaged cells were unable to maintain volume. They swelled markedly, lost Mg2+ and K+ and exhibited structural defects in the plasma membrane of the sarcolemma. These observations establish that loss of cell volume regulation is one of the early events associated with the development of irreversibility in severe myocardial ischemic injury.

Acute Disease↗
PubMed1976

Intractable renovascular hypertension in an adult recipient of a pediatric cadaveric renal transplant.

Renovascular hypertension developed in an anephric 37-year-old patient after he received a cadaveric renal transplant from a 2-year-old donor. Despite adequate homograft function, a transplant nephrectomy was perfomed because of intractable, lifethreatening hypertension. There was relative stenosis throughout the course of the transplanted renal artery. Pathologic examination of the kidney did not demonstrate evidence of technical failure or immunological or hypertensive damage. Atrophic changes in the media of the renal artery may have resulted from radiation damage. The hypertension appears to have been caused by disproportionate growth between the parenchyma in the hypertrophying pediatric homograft and its renal artery.

Adult↗
PubMed1976

Reduction of experimental myocardial infarct size with hyperosmolar mannitol.

Hypertonic mannitol previously has been shown to improve cardiac function, increase collateral flow, and decrease epicardial ST segment elevation following coronary occlusion in anesthetized or awake dogs. The present study quantitates by morphologic techniques, the effect of hypertonic mannitol on infarct size. Ischemic injury was produced by proximal occlusion of the circumflex artery for 40 min and necrosis was assessed after 48 hr of reflow. One group of dogs was given isotonic saline and the other hypertonic mannitol beginning the infusions just prior to, during, and for a short period after the release of the circumflex coronary artery occlusion. Serum osmolality increased by approximately 40 mOsm in the mannitol group. The administration of hypertonic mannitol was associated with a 40-50% reduction in infarct size ventricular fibrillation during occlusion and following release of the circumflex coronary artery occlusion was greater in mannitol-treated dogs although the difference was not statistically significant. Thus, the data obtained in this study extend previous observations and provide direct evidence that hypertonic mannitol can reduce infarct size in dogs with temporary circumflex artery occlusion and reflow.

Animals↗
PubMed1976

Mitochondrial structure and function in acute myocardial ischemic injury.

Changes in both the structure and function of mitochondria occur in the dog heart as a consequence of severe ischemia produced by acute coronary occlusion. Brief periods of severe ischemia (reversible injury) produced no significant change in mitochondrial ultrastructure and no defects in pyruvate or succinate metabolism. However, periods of ischemia of 40-60 minutes' duration (irreversible injury) produced striking structural changes including swelling, an increase in matrix space, disorganization of cristae, and the appearance of amorphous matrix densities. After 60 minutes of severe ischemia, one or more amorphous densities were present in each mitochondrial profile. These osmiophilic structures contained lipid but have not been characterized further. Their presence was typical of the irreversible state. Mitochondria of irreversibly injured cells were fragile, and consequently were more difficult to isolate than mitochondria of control tissue. Furthermore, after isolation from tissue injured by 60 minutes of ischemia, they showed markedly defective function.

Animals↗
PubMed1975

Distribution of coronary arterial flow in acute myocardial ischemia.

Thioflavin S (TS), a fluorescent dye, was used to visualize the distribution of coronary flow within the area of ischemia produced by circumflex artery occlusions. In the ischemic region, TS failed to penetrate the subendocardium and was seen in the subepicardium. Even though collateral flow was noted in the subepicardium, studies with methylene blue showed that it was inadequate to prevent the development of ischemia. The proportion of the posterior papillary muscle and subjacent myocardium showing TS nonfluorescence was similar after 15 and 60 minutes of ischemia and correlated with maximum lead II ST segment elevation and the percent of grossly injured myocardium found at 60 minutes postocclusion. The results suggest that flow to ischemic myocardium is reduced to the greatest extent in the subendocardium, ie, the site where irreversible injury first appears.

Acute Disease↗
PubMed1975

Ischemic tissue injury.

The subendocardial to subepicardial gradient in the severity of ischemia following acute coronary occlusion is described. The effects of mild, moderate, and severe ischemia on cell structure and function are compared in summary form, and special attention is given to the effects of severe ischemia on myocardial cells. The characteristics of reversible and irreversible ischemic injury are defined in biologic terms. The failure of cell volume regulation in cells which have entered an irreversible state of ischemic injury is demonstrated by the use of free-hand slices in vitro. Irreversibility is associated with structural defects in the plasma membrane and is reflected in an increased slice inulin-diffusible space, increased slice H2O and Na+ content, and failure of the tissue to maintain the high K+ and Mg2+ levels characteristic of normal left ventricular myocardium. Defective cell membrane function is an early feature of irreversible ischemic injury and may be a primary event in the genesis of the irreversible state.

Animals↗
PubMed1975

Demonstration of the "no-reflow" phenomenon in the dog heart after temporary ischemia.

The effect of 40- or 90-min periods of temporary myocarardial ischemia on the distribution of coronary flow and capillary structure were assessed in groups of mongrel dogs. Thioflavin S. a fluorescent dye which stains vascular endothelium when injected intravenously, was used to demonstrate the distribution of microvascular perfusion at 10 sec, 5 min, or 20 min following release of a 40-or 90min circumflex coronary artery occlusion. Hearts which demonstrated perfusion defects were sampled for electron microscopy. Following 40 min of occlusion, thioflavin S was distributed uniformly throughout the myocardium. In contrast, following 90-min periods of coronary occlusion, perfusion defects always were present in the subendocardial half of the posterolateral left ventricular wall. Several morphological features in these areas of no reflow were observed by electron microscopy, including decreased endothelial pinocytotic vesicles, endothelial gaps and bleb formation, capillaries packed with erythrocytes, occasional intraluminal thrombi, and extravascular erythrocytes and fibrin. Myocardial cells showing severe injury always were seen within but also extended beyond the areas of poor perfusion. These results demonstrate that areas of no reflow occur following 90-min periods of ischemic injury in the dog, but that primary myocardial cell injury occurs during the ischemic period and not as a function of the "no-reflow" phenomenon.

Animals↗
PubMed1975

Irreversible myocardial injury in anoxic perfused rat hearts.

Isolated rat hearts were perfused at 37 C on a double reservoir, nonrecirculating Langendorff apparatus. For aerobic perfusion, Krebs-Henseleit medium containing 10 mM glucose was gassed with 95% O2-5% CO2; for anoxic perfusion, glucose was replaced with 10 mM mannitol, a nonmetabolizable substrate, and the medium was equilibrated with 95% N2-5% CO2. Heart effluent was serially collected during perfusion for creatine phosphokinase activity (CPK) analysis. Fixation was with 1% glutaraldehyde for morphologic studies. With aerobic control perfusion, hearts continued contracting, released no CPK, and were morphologically normal by light and electron microscopy examination after 120 minutes. With anoxic perfusion, contractions soon ceased, and by 60 minutes a sustained slow release of CPK was first observed. By electron microscopy, cells at 60 or 90 minutes were swollen and contained amorphous matrix densities in mitochondria; a few cells showed breaks in cell plasma membrane. When anoxic hearts were challenged with reoxygenation, there was a sudden change in color to a pale opaque appearance, CPK was rapidly released, and there was massive cellular swelling. By electron microscopy, damaged cells showed contraction bands, clumping of nuclear chromatin, both amorphous densities and granular dense bodies in mitochondria, and prominent disruptions of cell plasma membranes. The number of damaged cells observed increased as a linear function of time between 30 and 55 minutes of anoxia. The results show that anoxic perfusion in vitro produces irreversible myocardial injury and that this injury is closely associated with loss of cell volume control, release of intracellular enzymes, and striking structural defects in the plasma membrane of the sarcolemma. Reoxygenation accelerates the development of lesions in irreversibly injured cells but protects reversibly injured cells.

Animals↗
PubMed1974

The "no-reflow" phenomenon after temporary coronary occlusion in the dog.

The role of microvascular damage in the genesis of the "no-reflow" phenomenon was investigated in the left ventricular myocardium of dogs subjected to temporary occlusions of a major coronary artery for 40 and 90 min. Intravenous carbon black or thioflavin S (a fluorescent vital stain for endothelium) were used to demonstrate the distribution of coronary arterial flow in control and damaged myocardium. These tracers were injected simultaneously with release of the coronary occlusion or after 5 or 20 min of reflow of coronary arterial blood. After 40 min of ischemia plus arterial reperfusion, usually the tracers were evenly distributed throughout the damaged tissue at each time of reperfusion. On the other hand, when reflow was allowed after 90 min of ischemia, portions of the inner half of damaged myocardium were not penetrated by the tracers. Electron microscopic study of this poorly perfused tissue revealed severe capillary damage; endothelial cells with large intraluminal protrusions and decreased pinocytic vesicles were common. Also, occasional intraluminal fibrin thrombi were noted, as well as extravascular fibrin deposits and erythrocytes. Myocardial cells were swollen in both poorly perfused and well-perfused irreversibly injured tissue. Contraction bands and mitochondrial Ca(2+) accumulation were prominent features of irreversible injury with reflow at 40 min but were not noted after 90 min of ischemia in areas with poor perfusion. These results suggest that 40 min of ischemia were tolerated by the capillary bed of the dog heart without serious capillary damage or perfusion defects, but that 90 min of ischemic injury was associated with the "no-reflow" phenomenon, i.e., failure to achieve uniform reperfusion. This failure of reflow was associated with extensive capillary damage and myocardial cell swelling. Death of severely ischemic myocardial cells in this model occurs before the onset of capillary damage and the no-reflow phenomenon.

Animals↗
PubMed1974

Effect of a transient period of ischemia on myocardial cells. I. Effects on cell volume regulation.

The effect of temporary periods of ischemia on the electrolytes and water of myocardial cells were studied in groups of mongrel dogs. Myocardial tissue exposed to 40 minutes of ischemia induced by occlusion of the circumflex branch of the left coronary artery developed no changes in water or electrolytes when compared to nonischemic left ventricle of the same or sham-operated animals, even though this period of ischemia is known to produce irreversible injury to many of the damaged cells. However, reperfusion of the affected myocardium with arterial blood for only 2 minutes resulted in striking increases in tissue H(2)O, Na(-), Cl(-) and Ca(2-). These changes in electrolytes increased in severity with longer periods of reflow, and tissue K(+) was decreased significantly after 10 minutes of reflow had passed. Analysis of the results suggested that the tissue edema was primarily the result of cellular swelling. Myocardium exposed to 15 minutes of ischemia followed by 2 minutes of reflow showed no significant changes aside from a slight increase in Na(+). These studies demonstrate that defects in cell volume regulation occur early in severe ischemic injury.

Animals↗
PubMed1974

Effect of a transient period of ischemia on myocardial cells. II. Fine structure during the first few minutes of reflow.

Changes produced in the posterior papillary muscle of the dog following 40 minutes of circumflex artery occlusion and 0 to 20 minutes of blood reflow were studied by electron miroscopy. With no reflow of blood, myocardial cells were modestly swollen, contained amorphous matrix densities in the mitochondria, had aggregation and margination of nuclear chromatin and relaxation of myofibrils. With as little as 2 minutes of blood reflow, cells developed contraction bands and were greatly swollen due to a generalized increase in sarcoplasmic space, formation of vacuoles and swelling of mitochondria. Frequently, cell membranes were lifted away from the myofibers, forming large subsarcolemmal blebs which appeared capable of compressing adjacent capillaries. The extracellular space did not appear to be enlarged, and the marked tissue edema found after reflow was due primarily to accumulation of intracellular fluid. In addition to explosive cell swelling, there was, over the 2- to 20-minute period of reflow, a progressive increase in size and number of granular mitochondrial dense bodies of the calcium accumulation type. No significant changes in lysosomes were observed. The speed with which the morphologic changes developed during very early reflow periods suggests that irreversible ischemic injury produces a defect in cell volume regulation during the phase of ischemia and that this defect becomes manifest if arterial flow is restored to the affected cells.

Animals↗