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R W Jeremy

Publications and source records attributed to R W Jeremy.

30 records · Page 2Linked to original sources
PubMed1993

The functional recovery of post-ischemic myocardium requires glycolysis during early reperfusion.

Glycolysis normally provides only a small fraction of myocardial ATP production, but ATP from glycolysis may be preferentially used to support membrane activities such as ion pumping. Since ion homeostasis is disturbed during ischemia, glycolysis may be particularly important in the recovery of postischemic myocardium. This hypothesis was investigated in isovolumic, isolated rabbit hearts, perfused with 16 mM glucose, 5 mM pyruvate or 5 mM acetate. Global left ventricular function (rate-pressure product, RPP) and unidirectional ATP synthesis rate (P(i)-->ATP flux, 31P NMR) were measured before and after 20 min global ischemia. Control hearts with intact glycolysis were compared with hearts which had glycolysis inhibited by iodoacetate (150 microM), 2-deoxyglucose (10 mM) or prior glycogen depletion. In normal hearts, inhibition of glycolysis had no effect on function when pyruvate or acetate was present as as a carbon substrate. In post-ischemic hearts, reperfusion with glucose (n = 7) resulted in moderate recovery of function to about 65% of pre-ischemic levels after 1 h reperfusion. Administration of iodoacetate at the onset of reperfusion to hearts receiving pyruvate or acetate resulted in much worse functional recovery and a marked rise in left ventricular end-diastolic pressure (LVEDP). With pyruvate (n = 7), RPP recovered to 27% of pre-ischemic levels, while mean LVEDP increased to 34 mmHg (vs 16 mmHg with glucose); with acetate (n = 6), RPP returned to 31% of pre-ischemic levels, while mean LVEDP rose to 32 mmHg. The ratio of P(i)-->ATP flux to atoms of oxygen consumed (P:O ratio) was 2.14 +/- 0.36 in hearts reperfused with iodoacetate and pyruvate, consistent with partial mitochondrial uncoupling. However, if inhibition of glycolysis with iodoacetate was delayed until after 30 min reperfusion, recovery of hearts reperfused with pyruvate was similar to hearts perfused with glucose, and there was no evidence of mitochondrial uncoupling (P:O ratio = 2.95 +/- 0.33). Inhibition of glycolysis during reperfusion with 2-deoxyglucose yielded results similar to reperfusion with iodoacetate. The worst recovery was observed in hearts with combined glycolytic inhibition by pre-ischemic glycogen depletion and iodoacetate during reperfusion (RPP = 13% of pre-ischemic levels). These findings indicate that glycolysis plays a crucial role during early reperfusion in the functional and metabolic recovery of post-ischemic myocardium.

Adenosine Triphosphate↗
PubMed1992

Relation between glycolysis and calcium homeostasis in postischemic myocardium.

This study examined the hypothesis that glycolysis is required for functional recovery of the myocardium during reperfusion by facilitating restoration of calcium homeostasis. [Ca2+]i was measured in isolated perfused rabbit hearts by using the Ca2+ indicator 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5F-BAPTA) and 19F nuclear magnetic resonance spectroscopy. In nonischemic control hearts, inhibition of glycolysis with iodoacetate did not alter [Ca2+]i. In hearts subjected to 20 minutes of global zero-flow ischemia, [Ca2+]i increased from 260 +/- 80 nM before ischemia to 556 +/- 44 nM after 15 minutes of ischemia (p less than 0.05). After reperfusion with 5 mM pyruvate as a carbon substrate, [Ca2+]i increased further in hearts with intact glycolysis to 851 +/- 134 nM (p less than 0.05 versus ischemia) during the first 10 minutes of reperfusion, before returning to preischemic levels. In contrast, inhibition of glycolysis during the reperfusion period resulted in persistent severe calcium overload ([Ca2+]i, 1,380 +/- 260 nM after 15 minutes of reperfusion, p less than 0.02 versus intact glycolysis group). Furthermore, despite the presence of pyruvate and oxygen, inhibition of glycolysis during early reperfusion resulted in greater impairment of functional recovery (rate/pressure product, 3,722 +/- 738 mm Hg/min) than did reperfusion with pyruvate and intact glycolysis (rate/pressure product, 9,851 +/- 590 mm Hg/min, p less than 0.01). Inhibition of glycolysis during early reperfusion was also associated with a marked increase in left ventricular end-diastolic pressure during reperfusion (41 +/- 5 mm Hg) compared with hearts with intact glycolysis (16 +/- 2 mm Hg, p less than 0.01). The detrimental effects of glycolytic inhibition during early reperfusion were, however, prevented by initial reperfusion with a low calcium solution ([Ca]o, 0.63 mM for 30 minutes, then 2.50 mM for 30 minutes). In these hearts, the rate/pressure product after 60 minutes of reperfusion was 12,492 +/- 1,561 mm Hg/min (p less than 0.01 versus initial reflow with [Ca]o of 2.50 mM). These findings indicate that the functional impairment observed in postischemic myocardium is related to cellular Ca2+ overload. Glycolysis appears to play an important role in restoration of Ca2+ homeostasis and recovery of function of postischemic myocardium.

Animals↗
PubMed1990

Progressive failure of coronary flow during reperfusion of myocardial infarction: documentation of the no reflow phenomenon with positron emission tomography.

During reperfusion of a myocardial infarct, development of microvascular occlusion may result in regional hypoperfusion ("no reflow") despite a patent infarct-related artery. This study examined the extent and time course of no reflow with use of rubidium-82 positron emission tomography. In 12 anesthetized dogs, the left anterior descending coronary artery was occluded for 90 min and then freely reperfused. Regional myocardial perfusion was imaged by serial rubidium-82 positron emission tomography during coronary occlusion and every 30 min during reperfusion. After 4 h of reperfusion, infarct size and no reflow zone were measured postmortem by triphenyltetrazolium and thioflavin staining, respectively. Perfusion defects evident on rubidium-82 images during coronary occlusion rapidly resolved during the early reflow period. However, a recurrent perfusion defect appeared after 1 to 2 h of reflow in all dogs. The severity of recurrent perfusion defects progressed with time; after 5 min of reflow, relative perfusion in the left anterior descending artery territory was 97 +/- 6% of that in the normal circumflex artery region, but perfusion decreased progressively to 68 +/- 5% after 2 h (p less than 0.05) and to 55 +/- 4% after 4 h of reperfusion (p less than 0.05 versus 2 h). As measured by radioactive tracer microspheres, endocardial blood flow decreased similarly in the postischemic left anterior descending artery region from 1.2 +/- 0.2 ml/min per g after 5 min of reflow to 0.4 +/- 0.1 ml/min per g after 3 h of reflow (p less than 0.01). Residual infarct perfusion, measured by rubidium-82 after 4 h of reflow, was related to both infarct size (r = -0.88) and the extent of the no reflow zone (r = -0.84) in the postmortem left ventricular sections. Thus, serial positron emission tomography with rubidium-82 demonstrates a progressive loss of infarct perfusion, beginning 1 to 2 h after initial restoration of blood flow despite patency of the infarct-related artery. This phenomenon is probably a manifestation of progressive microvascular occlusion within the reperfused myocardium.

Animals↗
PubMed1990

Wiener filtering improves quantification of regional myocardial perfusion with thallium-201 SPECT.

Quantitation of myocardial perfusion with thallium-201 (201Tl) SPECT is limited by finite resolution and image noise. This study examined whether Wiener filtering could improve quantitation of the severity of myocardial perfusion deficits. In 19 anesthetized dogs, adjustable stenoses were placed on the left anterior descending (LAD, n = 12) or circumflex (LCx, n = 7) arteries. Thallium-201 SPECT images were acquired during maximal coronary vasodilation with dipyridamole, and simultaneous measurements of myocardial blood flow were made with microspheres. The relationship between SPECT and microsphere flow deficits in the LAD region was significantly better (p less than 0.05) with Wiener filtering (Y = 0.90X + 0.03, r = 0.78) than with conventional Hanning filtering (Y = 0.66X + 0.34, r = 0.61). Similarly, in the LCx region the relationship between SPECT and microsphere perfusion deficits was better (p less than 0.01) with the Wiener filter (Y = 0.91X + 0.07, r = 0.66) than with the Hanning filter (Y = 0.36X + 0.50, r = 0.40). Wiener filtering improves quantitation of the severity of regional myocardial perfusion deficits, allowing better assessment of the functional significance of coronary artery stenoses.

Animals↗
PubMed1989

Neutrophil depletion does not prevent myocardial dysfunction after brief coronary occlusion.

Recent evidence suggests that oxygen free radicals generated during ischemia or reperfusion may contribute to myocardial dysfunction after brief coronary occlusion ("myocardial stunning"). Because neutrophil leukocytes represent a potential source of oxygen radicals, the concept of whether depletion of neutrophils could attenuate myocardial stunning after 10 min of ischemia was examined. In 16 anesthetized dogs, the left anterior descending coronary artery was perfused by an extracorporeal circuit, either with (n = 8) or without (n = 8) neutrophil filters in the perfusion line. The group with filters had near total absence of neutrophils in blood perfusing the left anterior descending coronary artery territory (16 +/- 8 versus 1,826 +/- 399/microliters in the control group). Systolic myocardial shortening and end-systolic pressure-segment length relations were recorded during rest conditions and during incremental intracoronary infusion of dobutamine (5 to 15 micrograms/min) before and after 10 min of coronary flow occlusion. Before coronary occlusion, systolic myocardial shortening at rest was similar in control (15.4 +/- 1.7%) and neutropenic (12.4 +/- 2.2%) groups. Dobutamine (15 micrograms/min) resulted in increased shortening in both control (18.2 +/- 1.4%, p less than 0.01) and neutropenic (15.8 +/- 1.5%, p less than 0.05) groups and in a leftward shift of the end-systolic pressure-length relation. During coronary occlusion, collateral coronary flow to the left anterior descending coronary artery territory was not significantly different in the control (0.10 +/- 0.03 ml/min per g) and neutropenic (0.18 +/- 0.06 ml/min per g) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Patterns of left ventricular dilation during the six months after myocardial infarction.

Changes in left ventricular volume after a first myocardial infarction were studied in 50 patients. Serial radionuclide angiograms were obtained 48 h, 10 days and 1 and 6 months after infarction and left ventricular volume measured by a nongeometric method. Left ventricular dilation (greater than or equal to 20% increase in end-diastolic volume) occurred within 10 days of infarction in 11 patients, who had a mean volume increase of 34 +/- 15% (p = 0.002 versus 48 h) at 10 days and 61 +/- 43% (p = 0.01 versus 10 days) at 6 months. Ten other patients manifested left ventricular dilation between 10 days and 6 months with a lesser volume increase of 42 +/- 18% by 6 months. Among the 21 patients with ventricular dilation, progressive dilation (serial volume increases greater than or equal to 20% on two or more occasions) occurred in 8 patients, who all had a large anterior infarct. Mean volume increases at 10 days and 1 and 6 months were 27 +/- 20%, 49 +/- 40% (p = 0.03 versus 10 days) and 79 +/- 37% (p = 0.006 versus 1 month), respectively, in this group. In patients with progressive dilation, left ventricular ejection fraction decreased from 35 +/- 6% at 48 h to 24 +/- 10% at 1 month (p less than 0.001) and 27 +/- 10% (p = 0.006) at 6 months. Between 1 month and 2 years after infarction six patients died, of whom four had progressive dilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Preservation of coronary flow reserve in stunned myocardium.

Microvascular obstruction and persistent focal ischemia have been suggested as a possible cause of myocardial dysfunction (stunning) after brief coronary occlusion. Microvascular occlusion should result in a reduction in maximal coronary flow reserve, although resting transmural coronary flow may be maintained by release of local vasodilators, such as adenosine. To test the microvascular occlusion hypothesis, coronary flow reserve was measured in 14 anesthetized dogs, before and after myocardial stunning produced by 10 min of ischemia. Intracoronary adenosine infusion (5,900 microM/min) increased coronary flow to the same degree in normal [195 +/- 20 (SE) ml/min] and stunned (212 +/- 23 ml/min) myocardium. Peak hyperemic flow after 100 s of coronary occlusion was also similar in normal (205 +/- 25 ml/min) and stunned (218 +/- 23 ml/min) myocardium. The adenosine antagonist 8-phenyltheophylline (5 mg/kg) reduced the flow response to exogenous adenosine, but neither resting coronary flow nor peak hyperemic flow in stunned myocardium was altered. In stunned myocardium, myocardial shortening at rest (0.2 +/- 2.0%) increased during reactive hyperemia (to 13.8 +/- 2.5%, P less than 0.01), but shortening promptly returned to basal levels after each hyperemia. These findings indicate that fixed microvascular occlusion is unlikely to be an important factor in the pathogenesis of stunned myocardium and that local adenosine release does not appear to have a compensatory role in coronary vasoregulation in stunned myocardium.

Adenosine↗
PubMed1989

Neutrophil depletion limited to reperfusion reduces myocardial infarct size after 90 minutes of ischemia. Evidence for neutrophil-mediated reperfusion injury.

Reperfusion of ischemic myocardium may accelerate necrosis of injured myocytes. To determine the role of neutrophil leukocytes in this process, we examined whether neutrophil depletion during reperfusion could modify infarct size in anesthetized dogs. The proximal circumflex coronary artery was occluded for 90 minutes and then reperfused for 2 hours via an extracorporeal circuit with either whole blood (n = 11) or with blood depleted of neutrophils by leukocyte filters (n = 11). The leukocyte filters caused near-total neutropenia in blood reperfusing the ischemic myocardium (7 +/- 7 neutrophils/microliters compared with 2,551 +/- 317/microliters in controls, mean +/- SEM; p less than 0.001. Infarct size was measured by planimetry of myocardial slices stained with triphenyltetrazolium chloride (TTC), and the accuracy of TTC for identifying necrotic myocardium was verified by electron microscopy. The size of the ischemic risk region was the same in the control (41.6 +/- 1.0%) and neutropenic (41.8 +/- 2.1%) groups. Collateral blood flow to the risk region was the same in control (0.15 +/- 0.03 ml/min/g) and neutropenic (0.13 +/- 0.03 ml/min/g) groups. Among dogs with collateral flow less than 0.2 ml/min/g, infarct size was reduced in the neutropenic group (27.7 +/- 6.7% of risk region, n = 8), compared with control dogs (52.5 +/- 5.7%; n = 7; p = 0.02). Multiple linear regression described the relation between infarct size, risk region size, and collateral flow in the control group, and the same regression relation was used to predict infarct size for the neutropenic group. Mean predicted infarct size in the neutropenic group (n = 11) was 16.8 +/- 3.4% of left ventricle, whereas mean observed infarct size was 9.6 +/- 3.1% (p less than 0.01). The extent of the no-reflow zone (absence of thioflavin-S-fluorescence) was also less in the neutropenic than the control group (2.2 +/- 0.8% vs. 8.1 +/- 2.7% of the risk region, p less than 0.05). Neutropenia limited to the reperfusion period is associated with significant reductions in the extent of the infarct and no-reflow zones after 90 minutes of ischemia. These findings support the hypothesis that reperfusion necrosis occurs after prolonged myocardial ischemia and indicate that neutrophil leukocytes are important mediators of such reperfusion injury.

Animals↗
PubMed1989

Coronary pressure-flow relations in hypertensive left ventricular hypertrophy. Comparison of intact autoregulation with physiological and pharmacological vasodilation in the dog.

Coronary pressure-flow relations during autoregulated and vasodilated flow states were compared between eight dogs with renovascular hypertension and left ventricular hypertrophy and 12 normal dogs. Each relation was constructed from serial steady-state measurements of end-diastolic coronary pressure and flow during perfusion of the circumflex artery by an extracorporeal circuit at controlled diastolic pressures of 20-200 mm Hg. Autoregulated pressure-flow relations were compared at three levels of myocardial oxygen demand: resting, high (dobutamine 10 micrograms/kg/min), and low (propranolol 2.5 micrograms/kg/min). Autoregulatory capacity was assessed by calculation of closed-loop flow gain. At each level of myocardial oxygen demand, the lower limit of autoregulation occurred at higher perfusion pressures in the hypertrophy group (rest 65 +/- 3, high 92 +/- 4, low 66 +/- 4 mm Hg) than in the normal group (rest 53 +/- 2, p less than 0.05; high 75 +/- 5, p less than 0.05; low 51 +/- 3 mm Hg) (p less than 0.05). Maximum autoregulatory gain was similar in the normal and hypertrophy groups during resting and low myocardial oxygen demand but was reduced in the hypertrophy group during dobutamine studies. When coronary flow decreased below the lower limit of autoregulation, systolic shortening was reduced in both normal and hypertrophy groups. However, as the autoregulatory limits were at higher pressures in the hypertrophy group, shortening in this group deteriorated at perfusion pressures that did not affect the normal heart. Coronary pressure-flow relations during physiological (peak hyperemia after 15-second flow occlusion) and pharmacologica (intracoronary adenosine 400 micrograms/min) vasodilation was curvilinear and fitted by quadratic regression. During hyperemic vasodilation, maximal conductance per unit mass of myocardium was less in the hypertrophy group over a wide range of perfusion pressures. At a diastolic perfusion pressure of 80 mm Hg, maximum conductance was 4.6 +/- 0.5 ml/min/100 g/mm Hg in the normal group and 3.4 +/- 0.4 ml/min/100 g/mm Hg (p less than 0.05) in the hypertrophy group. Intracoronary adenosine elicited further vasodilation in both groups, but maximum conductance remained less in the hypertrophy group (8.5 +/- 1.7 ml/min/100 g/mm Hg at a perfusion pressure of 80 mm Hg) than in the normal group (13.5 +/- 2.0 ml/min/100 g/mm Hg) (p less than 0.05). Maximal coronary flow reserve is reduced in left ventricular hypertrophy, with a consequent shift of the lower limit of autoregulation to higher perfusion pressures. Thus, as coronary perfusion pressure is decreased, coronary flow and myocardial shortening become impaired at higher

Animals↗
PubMed1987

Infarct artery perfusion and changes in left ventricular volume in the month after acute myocardial infarction.

The relation between perfusion of the infarct-related artery and changes in left ventricular volume and function during the month after a first myocardial infarction was examined in 40 patients who did not receive thrombolytic therapy. Infarct artery perfusion was documented at predischarge coronary angiography, and left ventricular volume was measured by nongeometric analysis of radionuclide angiograms performed within 48 hours of infarction and at 1 month. Left ventricular dilation (greater than or equal to 20% increase in volume) developed in 16 patients, whereas 5 patients had a decrease in left ventricular volume of greater than or equal to 20% by 1 month. Left ventricular dilation occurred in all 14 patients without perfusion of the infarct-related artery, compared with only 2 of 26 patients with perfusion of this artery due to subtotal occlusion or collateral vessels. All five patients whose left ventricular volume decreased by greater than or equal to 20% had a perfused infarct artery. Multiple linear regression analysis confirmed that the degree of perfusion of the infarct artery (partial r = 0.58, p = 0.001) was a more important predictor of volume change than was infarct size measured by peak creatine kinase (partial r = 0.30, p = 0.009) or QRS score (partial r = 0.20, p = 0.087). Left ventricular ejection fraction decreased from 0.38 +/- 0.10 to 0.30 +/- 0.16 (p = 0.05) in 11 patients with an anterior infarct and ventricular dilation; it increased from 0.45 +/- 0.10 to 0.62 +/- 0.07 (p = 0.02) in the 5 patients with a greater than or equal to 20% decrease in volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Effects of left ventricular diastolic pressure on the pressure-flow relation of the coronary circulation during physiological vasodilatation.

A study to analyse the effects of left ventricular diastolic pressure on coronary pressure-flow relations during physiological vasodilatation was carried out in 14 anaesthetised dogs. The left circumflex artery was perfused at controlled pressures via an extracorporeal circuit and vasodilatation induced by 15 s occlusion of coronary flow. The relation between end diastolic coronary perfusion pressure and flow at peak hyperaemia was linear above 40 mmHg (group 1, n = 7) and became curvilinear at perfusion pressures below 40 mmHg (group 2, n = 7). At a mean left ventricular end diastolic pressure of 8.6(0.8) mmHg the mean zero flow intercept (Pint) in group 1 was 22.5(2.3) mmHg. Graded increases in left ventricular end diastolic pressure by infusion of blood resulted in a parallel rightward shift of the vasodilated pressure-flow relation (Pint = 1.06 X LVEDP + 13.8 mmHg, r = 0.87). The curvilinear relations at low perfusion pressures in group 2 had lower zero flow intercept pressures (Pint = 4.8(0.7) mmHg at left ventricular end diastolic pressure 6.6(1.5) mmHg). As with group 1, graded increases in left ventricular end diastolic pressure caused a rightward shift of the pressure-flow relation, with a direct relation between left ventricular end diastolic pressure and zero flow intercept (Pint = 0.93 X LVEDP + 3.9 mmHg, r = 0.89). Diastolic coronary pressure-flow relations during physiological vasodilatation are essentially linear at perfusion pressures greater than 40 mmHg but are appreciably curved at lower pressures. Increases in left ventricular end diastolic pressure cause a parallel rightward shift of the linear region of the pressure-flow relation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗