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Biomedical subjects

R B Jennings

Publications and source records attributed to R B Jennings.

At least 91 records · Page 5Linked to original sources
PubMed1983

High energy phosphates, anaerobic glycolysis and irreversibility in ischemia.

The effects of severe regional myocardial ischemia in vivo and total ischemia in vitro on energy production by anaerobic glycolysis in dogs are described. The critical feature of ischemic injury in terms of the adenine nucleotide pool is the fact that the demand of severely or totally ischemic tissue for HEP exceeds the capacity of the damaged myocytes to produce it. The consequent depletion of ATP to very low levels and the destruction of the adenine nucleotide pool are associated with, or may be casually related to, the loss of cellular viability.

Adenine Nucleotides↗
PubMed1983

Prolonged depletion of ATP because of delayed repletion of the adenine nucleotide pool following reversible myocardial ischemic injury in dogs.

Sixty-five percent of the ATP and 50% of the total adenine nucleotide (sigma Ad) pool is lost from the subendocardial myocardium after 15 min of severe ischemia induced by circumflex artery occlusion in open-chest dogs (12). In the present experiment, we assessed the effects of various periods of arterial reflow following 15 min of ischemic injury on resynthesis of ATP and sigma Ad. The circumflex artery was occluded for 15 min and reperfused for 20 or 60 min or 24 or 96 hr. The mean ATP after 15 min of ischemia was reduced 62% from 5.42 +/- 0.33 to 2.08 +/- 0.21 mumol/g; and the total nucleotide content was reduced by 50%. ATP content recovered slightly during the first 20 min of reperfusion but remained markedly depressed for at least 24 hr because of the initial depletion of adenine nucleotides and because minimal salvage of de novo repletion occurred in the injured muscle during this time period. By 4 days, ATP and total adenine nucleotides were still slightly depressed but had recovered to 88% and 91% of control. Electrolyte changes and an increased inulin-diffusible space, which are characteristic of irreversibly injured myocardium, reperfused for 20 or 60 min, were not observed. Also, tissue necrosis was absent in the hearts reperfused for 24 or 96 hr. These observations indicate that the marked depression of ATP and adenine nucleotides and the slow recovery of these metabolites occurred in myocardium that nevertheless was reversibly injured in terms of cellular viability.

Adenine Nucleotides↗
PubMed1983

Comparison of the effect of ischaemia and anoxia on the sarcolemma of the dog heart.

Contraction-band necrosis, a striking morphologic lesion, is common to many types of myocardial injury including the calcium paradox and ischaemic injury with reperfusion. This lesion is characterized by explosive swelling, massive calcium overload, and severe disruption of the myofibrils due to the formation of contraction bands. The studies reviewed in this paper provide evidence that in ischaemia and reperfusion, these changes are preceded by sarcolemmal injury that occurs during the period of ischaemia. Sarcolemmal injury was evaluated by electron microscopy and by measurements of inulin diffusible space (IDS) in thin slices of myocardium incubated in vitro. Reversibly injured ischaemic myocytes have ultrastructurally intact plasma membranes which are impermeable to inulin. Longer durations of ischaemia, sufficient to produce contraction-band necrosis during reperfusion, result in fragmentation of plasma membranes during the ischaemic intervals, and the IDS is markedly increased during subsequent incubation. Thus ultrastructural evidence of membrane damage is present early in ischaemia and is associated temporally with the increased IDS. The role of anoxia, per se, in inducing membrane damage was investigated in tissue slices incubated at 37 degrees C in crystalloidal media gassed with nitrogen. Anoxic slices produced lactate and lost ATP and adenine nucleotides, but cell volume and the IDS were not significantly increased for at least five hours (twice the time required for severe membrane damage to develop in total ischaemia) and the plasmalemma remained intact by electron microscopy. Thus, despite depletion of high energy phosphates, membrane damage, detectable by alterations in IDS or ultrastructure, occurs much more slowly during anoxia alone than during ischaemia. These results suggest that anoxia, per se, may not be the cause of membrane damage in ischaemia.

Animals↗
PubMed1981

Effect of coronary occlusion site on ischaemic bed size and collateral blood flow in dogs.

The ischaemic bed size (myocardium at risk) and collateral flow are major determinants of experimental myocardial infarct size. These parameters were compared in dogs with coronary occlusions at four commonly used sites. Regional blood flow was measured 5 min after proximal coronary occlusion of the circumflex (LCC) or anterior descending (LAD) arteries, or after distal occlusion of the LAD, or its apical branch. Occlusions were done sequentially in random order separated by 30 min intervals. The anatomic regions normally supplied by each occluded artery (ischaemic beds) were identified by simultaneous postmortem coronary perfusion with different coloured dyes. Proximal occlusions of the LCC and LAD produced equivalent areas of ischaemia (37 and 36% of the left ventricle) and these ischaemic beds had similar amounts of collateral flow (0.12 and 0.16 cm3.min-1.g-1). In comparison, distal LAD and apical branch occlusions involved 23 and 11% of the LV and collateral flow averaged 0.23 and 0.36 cm3.min-1.g-1. Thus, proximal LAD or LCC occlusion produce comparable areas of severe ischaemia. Experimental models using distal occlusions are characterised by more variable but often less severe ischaemia.

Animals↗
PubMed1981

Energy metabolism in the reversible and irreversible phases of severe myocardial ischemia.

In summary, myocardial ischemia is associated with the progressive depletion of HEP and the adenine nucleotide pool. Anaerobic glycolysis is essential for energy production in the severely ischemic myocyte and accounts for 80% of the HEP utilized by severely or totally ischemic myocardium. However, the rate of anaerobic glycolysis is too slow to prevent the progressive depletion of ATP. Anaerobic glycolysis stops entirely prior to the complete utilization of glycogen. Without remaining HEP stores or HEP production from anaerobic glycolysis, HEP utilization no longer can occur. This point occurs in vivo after about 40 minutes of severe ischemia and coincides with the onset of cell death. Modest depletion of ATP due to brief periods of transient ischemia may not cause cell death, but is associated with partial depletion of the adenine nucleotide pool. The slow repletion of this pool may be responsible for prolonged depression of contractile function.

Adenine Nucleotides↗
PubMed1981

Lethal myocardial ischemic injury.

The biologic changes occurring in severely ischemic myocytes in vivo as the affected cells pass through the phase of reversible to the phase of lethal or irreversible injury are reviewed with special emphasis on the effect of ischemia on the production and utilization of highenergy phosphate, the destruction of the adenine nucleotide pool, and the appearance of signs of damage to the plasma membrane of the sarcolemma. Evidence is presented that indicates that the events occurring in severe ischemia in vivo are essentially identical to those found in total ischemia in vitro except that the biologic changes of ischemia develop more slowly in total ischemia in vitro than in severe ischemia in vivo. The slower time course of injury, together with the uniformity of injury provided by total ischemia in vitro, may allow for more precise identification of potential lethal cellular events in ischemic injury. The production of highenergy phosphates (HEP) from anaerobic glycolysis have been estimated in both in vivo and in vitro ischemia by the measurement of lactate accumulation, and total HEP utilization has been estimated from the depletion of stores of preformed HEP. The results show that between 80% and 90% of the HEP utilized by ischemic dog left ventricle is produced by anaerobic glycolysis. The onset of irreversibility is associated with marked depletion of the HEP and adenine nucleotide pools of the tissue and the cessation of energy production via glycolysis. The cessation of anaerobic glycolysis may be caused by the low sarcoplasmic, adenosine triphosphate (ATP) concentration of the dying myocyte. In addition to the foregoing changes, irreversibly injured tissue exhibits both ultrastructural and functional evidence of disruption of the plasmalemma of the sarcolemma. The possible relationships, causal and otherwise, between severe HEP depletion and membrane damage are discussed. Both HEP depletion (ATP < 3-8% of control) and membrane damage are considered to be objective signs of the presence of irreversible myocardial ischemic injury. However, at the present time, there is no proof that these changes are causally related either to each other or to cell death in severe in vivo ischemia.

Adenine Nucleotides↗
PubMed1980

Tricuspid atresia with dextrotransposition, dextrocardia, and mitral insufficiency: successful circulatory correction.

A 13-year-old patient with visceral and atrial situs solitus, dextrocardia, dextro (D) transposition of the great vessels with subaortic conus, tricuspid atresia, massive mitral valve insufficiency, and previously performed pulmonary artery banding was seen at our hospital. A right atrial to pulmonary artery conduit procedure and mitral valve replacement successfully repaired this child's circulation.

Adolescent↗
PubMed1980

[Comparative study using colloidal lanthanum of defects in cardiomyocyte membrane permeability in deep ischemia and in isoproterenol exposure].

A comparative study of defects in permeability of contractile heart cell membranes in "calcium" necroses of the myocardium and "calcium-free" necroses developing in a focus of deep ischemia in experimental myocardial infarction was carried out. "Calcium" necroses of the myocardium were reproduced by inoculation of the experimental animals with toxic doses of isoproterenol. The time course of formation of permeability defects in the membranes correlated with the process of intracellular structural damage formation. Irrespective of the nature of the damaging factor, permeability of sarcolemma was found to be disturbed earlier than the appearance of defects in membranes of inner organelles. Various combinations of the toxic effect of excess calcium and oxygen deficiency determine specific features of morphogenesis of ultrastructural alterations in cardiomyocytes.

Animals↗
PubMed1979

The "wavefront phenomenon" of myocardial ischemic cell death. II. Transmural progression of necrosis within the framework of ischemic bed size (myocardium at risk) and collateral flow.

The present study was done to quantitate the evolution of myocardial ischemic cell death within the framework of (1) the anatomical boundaries of the ischemic bed at risk and (2) the magnitude and transmural distribution of collateral blood flow. Myocardial ischemia was produced by proximal circumflex (LCC) occlusions in open chest dogs. Infarcts reperfused at 40 minutes, 3 hours, or 6 hours were compared with permanent infarcts. All dogs were sacrificed at 4 days. Regional myocardial blood flow was measured with 9-micrometer tracer microspheres before, and 20 minutes after, LCC occlusion. The location and size of the ischemic LCC bed at risk was determined by a dye injection technique. Infarct size was quantitated from multiple histologic sections. Necrosis involved 28 per cent, 70 per cent, and 72 per cent of the ischemic bed at risk in infarcts reperfused at 40 minutes, 3 hours, and 6 hours versus 79 per cent following permanent LCC ligation. Viable and potentially salvageable subepicardial muscle persisted for at least 3 hours after the onset of ischemia. Most of the salvageable myocardium was in the subepicardial region. In all groups, the lateral margins of necrosis were sharp in the subendocardial zone and were determined by the anatomical boundaries of the ischemic LCC bed at risk. LCC bed size ranged from 29 to 48 per cent of the left ventricle and thus contributed to variation in infarct size. However, infarct size, as a percentage of bed size, was determined by the transmural extent of necrosis within that bed (r = -0.97). This transmural extent of necrosis was related to subepicardial collateral flow after 3 hours (r = 0.92) and 6 or 96 hours (r = -0.85) but not after 40 minutes (r = -0.26) of ischemia. Thus, irreversible injury of ischemic myocardium developed as a transmural wavefront, occurring first in the subendocardial myocardium but ultimately becoming nearly transmural. Eventual transmural necrosis, and therefore over-all infarct size was determined by, and can be predicted from flow measurements obtained shortly after coronary occlusion.

Animals↗