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Biomedical subjects

H F Downey

Publications and source records attributed to H F Downey.

At least 73 records · Page 4Linked to original sources

Small vessel and total coronary blood volume during intracoronary adenosine.

The effect of a maximally dilating dose of intracoronary adenosine on total (CBV) and small-vessel blood volume (MSVBV, an index of open-capillary density), hematocrit (MSVHct), and related parameters of O2 supply-demand ratio was examined in left ventricular myocardium of anesthetized open-chest dogs. CBV was measured from washout of 51Cr-labeled red blood cells (RBC) and MSVBV and MSVHct from contents of 51Cr-RBC and plasma label, either 131I-serum albumin or 59Fe-siderophilin, in samples of myocardium and blood. Coronary blood flow (CBF) was measured by electromagnetic flowmeter. Myocardial oxygen consumption (MVO2) was computed with the Fick equation. Myocardial oxygen tension (MPO2) was measured with bare-tipped platinum electrodes. Adenosine raised CBV 75%, CBF, 574%, and MPO2 122%, but did not affect significantly MSVBV, MSVHct, or MVO2. These results indicate that infusion of adenosine into a coronary artery perfused at constant pressure causes relaxation of smooth muscle of arteriolar resistance vessels and of other vessels larger than 100 micrometers diam, but not that of the precapillary sphincters. This may be explained by the opposing action of increased MPO2 on the sphincters when flow increases. MSVHct was consistently much less than large-vessel Hct. This warrants combined use of red blood cell and plasma labels for accurate measurements of MSVBV.

Adenosine↗

Shunting of microspheres across the canine coronary circulation.

Coronary shunting of 9 +/-1 micrometer and 25 +/- 5 micrometer radiolabeled microspheres was examined in anesthetized, open-chest dogs, whose left common coronary arteries were perfused at controlled pressures. Shunting was estimated from the difference in radioactivity between perfusion line and coronary sinus blood samples during selective elevations of coronary perfusion pressure (CPP), left ventricular afterload, and inspired oxygen. A linear relationship was found between coronary shunting of 9-micrometer microspheres and CPP over the range 100-200 mmHg. According to regression analysis, percent shunt flow was 4.0% at control CPP (100 mmHg) and 10.0% at CPP of 200 mmHg. No shunting of 25-micrometer microspheres occurred at any CPP. Raising afterload did not affect shunting at control CPP but attenuated the increase in shunting at elevated CPP. Changing inspired gas from room air to 100% oxygen did not influence shunting at control or elevated CPP. Raising CPP to 150 and 200 mmHg also released 2.5% and 5.9% of pretrapped 9-micrometer microspheres, respectively. This study demonstrates that vessels permitting passage of microspheres across coronary circulation are sensitive to elevated perfusion pressure.

Animals↗

Binding of (3H)dihydroalprenolol to beta adrenoceptors of cells isolated from adult rat heart.

Myocardial cells isolated from adult rat heart bind (3H)dihydroalprenolol. Sixty-one percent of this binding appeared to be at the beta adrenoceptors since it was inhibited by saturating quantities of the beta antagonist propranolol or by the beta agonist isoprenaline. The binding is stereoselective as the l-isomer of isoprenaline caused greater inhibition than the d-isomer. The binding of (3H)dihydroalprenolol to beta adrenoceptors was saturable; half maximum binding occurred at about 8 nM and full saturation at 30--40nM.

Alprenolol↗

Coronary reperfusion: effects of vasodilators (papaverine and adenosine).

Reperfusion of a coronary artery is followed by a decline of the myocardial blood flow to both the ischemic (reperfused) and border regions, and the appearance of a transmural flow gradient favoring the epicardium. These findings were ascribed to vascular changes in the reperfused coronary bed. The behavior of the myocardial blood flow was investigated (1) after 4 hours of reperfusion following the intracoronary infusion of vasodilators (papaverine and adenosine) and (2) following the intravenous administration of papaverine during the total period of reperfusion. Intracoronary infusion of vasodilators increased flow (147 per cent) to all the layers of the reperfused myocardium but failed to alter the transmural distribution of flow. The flow response to these vasodilators in the normal vascular bed consisted of a marked increase in flow (385 per cent) and a normal, uniform distribution, suggesting that the development of anatomical vascular changes reduced the capacity of the reperfused vasculature to increase flow, and that these changes were more marked in the endocardial layer. The intravenous papaverine infusion during reperfusion normalized the total flow and its distribution in the zone bordering the reperfused myocardium but not to the ischemic, suggesting perhaps that papaverine may be useful in protecting potentially salvageable myocardium.

Adenosine↗

Coronary hemodynamics during reperfusion following acute coronary ligation in dogs.

The coronary hemodynamic effects of re-establishing blood flow to ischemic myocardium and the regional distribution of myocardial flow during reperfusion were studied in anesthetized open-chest dogs. A large portion of the left ventricular wall was rendered ischemic by occlusion of the left anterior descending coronary artery for 2 hours. During reperfusion of the LAD, coronary resistance in the reperfused vasculature increased progressively for the first 3 hours, while resistance in the intact LC vasculature was unchanged. Minimal resistances in the reperfused vascular bed, calculated from mean aortic pressure and peak coronary reactive hyperemic blood flow following a 90 sec. LAD occlusion, were elevated significantly during reperfusion. The increased minimal resistance values, which reflect the passive physical component of resistance, indicate structural changes in the reperfused vascular bed which were evident shortly after the initiation of reperfusion and persisted throughout the experimental period. Coronary resistances (RH) in the reperfused (LAD) and intact (LC) vasculatures during the reactive hyperemia following 10 sec. coronary occlusions were evaluated. During reperfusion, RH in the reperfused vasculature increased progressively while RH in the intact bed was unchanged. The marked increase in RH in the LAD indicates that the reactive hyperemic flow response to a consistent period of coronary occlusion progressively diminished, and reflects a gradual reduction in the vasodilatory potential of the reperfused coronary circulation. The regional distribution of myocardial blood flow following 5 minutes, 2 hours, and 4 hours of reperfusion was measured with multiple injections of radioactive microspheres. These measurements demonstrated a progressive reduction of blood flow to the reperfused myocardium with no significant change in flow to the control myocardium. In contrast to the uniform transmural distribution of flow in the normal myocardium, the reperfused region showed a distinctly nonuniform distribution of flow after 2 hours and 4 hours of reperfusion, with more severe reduction of flow to the endocardial layer. These studies would suggest that rechannelling blood flow distal to an acute coronary occlusion in human subjects might not in itself be capable of reversing the myocardial injury. It is hoped that additional therapeutic measures might be applied to salvage the injured myocardium.

Animals↗

Dynamics of tissue distribution of radiopotassium as affected by simulated differences in regional extraction.

Simulation of tissue uptake and release of radiopotassium with a digital computer shows that tissue distribution of this diffusible indicator of regional blood flow will be essentially static during recirculation of the isotope despite large differences in regional extractions. Thus, the widely accepted view that static distribution results from homogeneous extractions may be invalid.

Computers↗

Myocardial and total body extractions of radiorubidium in anesthetized dogs.

Myocardium (EM) and average total body (ETB) extractions of 86-Rb were determined in 24 anesthetized, open-chest dogs. Blood from the coronary sinus and from the pulmonary artery reflected the uptake of 86-Rb by myocardium and the total body, respectively, and extractions were computed from the relative arteriovenous differences (A-V/A). While the arterial concentration of 86-Rb was constant, EM varied from 0.66 plus or minus .02 (SE) at 2-2.5 min to 0.65 plus or minus 0.02 at 5-5.5 min, and ETB varied from 0.63 plus or minus 0.01 to 0.58 plus or minus 0.01 over the same interval. Mean extractions were similar statistically at 2-2.5 min, but individual differences as great as 30% were encountered at the 95% confidence level. After 3 min of 86-Rb administration, EM significantly exceeded ETB (P is less than 0.05) due to the more rapid decline with time of ETB. The similarity of the early extractions of 86-Rb by myocardium and by the total body supports, in general, the use of the radiorubidium uptake method for measuring coronary blood flow. However, the administration of the indicator should be brief, and rather large errors in individual estimates must be anticipated.

Animals↗