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Biomedical subjects

R W Millard

Publications and source records attributed to R W Millard.

At least 73 records · Page 4Linked to original sources
PubMed1981

Mitochondrial inner membrane enzyme defects in porcine myocardial ischemia.

Left anterior descending coronary artery occlusion in anesthetized pigs produced a stable transmural ischemia characterized by a rapid and then sustained loss of blood flow and mechanical function. After 2 h of occlusion, mitochondria from the ischemic area exhibited a 36 +/- 6% drop in state 3 respiratory activity (QO2) supported by the NAD-linked substrates, glutamate plus malate, but only a 5 +/- 3% decrease in QO2 with succinate plus rotenone. The activity of electron transfer complex I (NADH-CoQ reductase) decreased commensurately by 33 +/- 4% with the decrease in QO2 with NAD-linked substrates. Consistent with the nearly unchanged QO2 with succinate plus rotenone, the activities of electron transfer complexes III and IV decreased only slightly by 9 +/- 5% and 9 +/- 4%, respectively. Mitochondrial ATPase (complex V) activity decreased by 48 +/- 2% with little change in its oligomycin sensitivity. A 48% drop in ATPase activity was shown, by means of oligomycin titrations, to correspond to a 32% decrease in NAD-linked substrate supported QO2. The decreases observed in NADH-CoQ reductase and ATPase activities each account nearly quantitatively for the impaired mitochondrial phosphorylating respiration observed during sustained myocardial ischemia. These results suggest that mitochondrial inner enzyme complexes I and V are important sites of cellular injury in myocardial ischemia.

Adenosine Triphosphatases↗
PubMed1980

Baroreflex sensitivity in an amphibian, rana catesbeiana, and a reptilian, Pseudemys scripta elegans.

An inverse relationship between heart rate and systematic arterial pressure is demonstrated in unanesthetized bullfrogs (Rana catesbeiana) and red-eared turtles (Pseudemys scripta elegans). Drug-induced elevation of systemic blood pressure resulted in proportional decreases in heart rate and lengthening of the pulse interval. Conversely, nitroglycerin-induced decreases in blood pressure produced compensatory increases in heart rate. This relationship in frogs is defined by y = 25.4x + 1684, and in turtles by y = 64.8x + 1686, where y is pulse interval in msec and x is systolic blood pressure in mmHg. Resting and drug-induced systolic pressure limits were not different in the two species. However, both resting and reflexly altered heart rates were significantly lower in turtles than in frogs (p < .05). The heart rate responses were abolished by atropinization, without effect on the blood pressure responses. While anatomic identification of the baroreceptor site sensing the pressure changes remains to be made, the translation of pressure information via reflex pathways analogous to mammalian baroreceptor reflex arc system is evidenced in these lower vertebrates.

Animals↗
PubMed1980

Skin circulation of the frog, Rana catesbeiana: distribution and dynamics.

The volume and distribution of blood flow to the skin of the bullfrog, Rana catesbeiana, from both the pulmocutaneous and systemic arterial sources were measured. Radioactively labelled microspheres (35 +/- 5 micron) were used to map the regional distribution of each of these sources and to measure the systemic blood flow to the skin during air breathing and diving. Cutaneous artery blood flow was measured with an ultrasonic (Doppler) flowmeter. The systemic supply to the skin perfuses predominantly the limbs, while the largest cutaneous artery supply is to the back and flanks of the animal. All regions received blood from both sources. The cutaneous artery blood flow decreased during diving to approximately one-third of the pre-dive level. This decrease, however, was offset by an approximately equivalent increase in systemic blood flow to the skin during diving. These data should reconcile the decrease in pulmocutaneous blood flow and the important function of the skin as a gas exchanger during diving.

Animals↗
PubMed1980

Responses of coronary collateral flow and dependent myocardial mechanical function to the calcium antagonist, diltiazem.

We sought to determine whether the calcium antagonist, diltiazem, increased regional myocardial collateral blood flow in a dog model in which the physiologic conditions thought to be associated with angina pectoris had been induced, and to determine if such changes would be reflected in alterations in function of the collateral-dependent myocardium. Regional myocardial function and blood flow were measured with instruments in dogs for weeks as the left circumflex artery was progressively stenosed to occlusion by an implanted ameroid constrictor. The extent of collateral development was determined in terms of the reduction in regional function induced by brief, total test occlusions. When collaterals had developed adequate for the metabolic requirements at rest, pacing tachycardia stress test produced ischemia-related hypofunction. Under these conditions, diltiazem, 20 mirogram/min/kg, increased blood flow via collateral channels from approximately 140 to 190 ml/min/100 g tissue (epicardium) and from 80 to 140 ml/min/100 g tissue (endocardium) in the colateral-dependent area without significant modification in hypofunction. Similar results were obtained in dogs with greater collateral flow reserve later in the collateral development process when the ameroid constrictor had completely occluded the vessel and stress testing did not produce hypofunction. Thus, diltiazem increased collateral flow to collateral-dependent myocardium under conditions simulating unstable angina pectoris.

Angina Pectoris↗
PubMed1979

Microsphere studies of bullfrog central vascular shunts during diving and breathing in air.

Bidirectional central vascular shunts were measured during diving and breathing in air in unanesthetized bullfrogs by using pulmonary trapping of 38 mu mean diameter radionuclide-labelled microspheres. Six animals studied during diving exhibited a strong overall right-to-left shunting pattern comprised of both a predominant (68% mean) right-to-left shunt and a weak (23%) left-to-right countershunt. Five animals with access to air showed a variety of distribution patterns, including predominant shunts in the left-to-right (1 animal) and right-to-left (1 animal) directions, nearly complete mixing (2 animals) and separation of systemic and pulmonary venous returns (1 animal).

Animals↗
PubMed1979

Prostaglandin control of the renal circulation in response to hypoxemia in the fetal lamb in utero.

We studied the effects of 10-minute periods of hypoxemia in unanesthetized fetal lambs in utero instrumented for measurements of arterial pressure and renal and iliac blood flows. Fetal hypoxemia, induced by delivering a hypoxic gas mixture to the ewe, was characterized by a reduction in fetal PaO2 from 20.1 +/- 1.4 to 8.8 +/- 1.0 mm Hg (mean +/- SE). The fetus responded with bradycardia and persistent vasoconstriction in the iliac bed throughout the 10-minute period. In contrast, renal resistance rose significantly only at the end of the hypoxemic period. After 5-7 minutes of hypoxemia, when iliac flow had fallen by 40 +/- 4% and iliac resistance had risen by 86 +/- 13%, renal flow and resistance were not changed significantly from control; in fact, we found that renal flow rose substantially at this time in several fetal lambs. After blockade of prostaglandin synthesis with either indomethacin or meclofenamate, renal flow fell after 5-7 minutes of hypoxemia by 36 +/- 5%. The reduction in renal flow and increases in renal resistance were significantly greater than was observed prior to blockade of prostaglandin synthesis. Thus, fetal hypoxemia elicits bradycardia and intense peripheral vasoconstriction reflected by the changes in the iliac bed, with relative sparing of the reanl bed. The relative protection of the renal bed during fetal hypoxemia appears to be related to a mechanism involving prostaglandins, since after blockade of prostaglandin synthesis, hypoxemia results in intense renal vasoconstriction.

Animals↗
PubMed1978

Acute coronary occlusion in the pig: effect of nitroglycerin on regional myocardial blood flow.

Myocardial blood flow was studied in 10 closed chest, anesthetized pigs after an acute balloon catheter occlusion of the left anterior descending coronary artery. With use of radioactive microspheres (15 mu), myocardial blood flow was measured before and during an intravenous nitroglycerin infusion and during a combined nitroglycerin-phenylephrine infusion. A significant zone of ischemis (myocardial blood flow less than 50 percent of normal zone flow) was produced by the occlusion and involved 15 percent of the combined left ventricular and interventricular septal mass. More than 50 percent of this ischemic zone was intensely ischemic (myocardial blood flow 0 to 3 percent of normal). Nitroglycerin resulted in a 20 to 30 mm Hg decrease in systolic blood pressure. Myocardial blood flow was unchanged in intensely ischemic areas but varied directly with the product of heart rate and systolic blood pressure in the moderately ischemic area (myocardial blood flow 26 to 50 percent of normal). S-T segment elevation was significantly increased during nitroglycerin infusion and returned to control level with the added infusion of phenylephrine sufficient to restore the systemic blood pressure to prenitroglycerin values. No improvement in ischemic zone perfusion could be demonstrated during the infusion of nitroglycerin alone or with phenylephrine. The endocardial-epicardial flow ratio in moderately ischemic areas was slightly lower than the normal zone flow ratio and decreased slightly during infusion of nitroglycerin. With the addition of phenylephrine, the ratios rose slightly and no longer differed from prenitroglycerin values. Blood flow distribution in acutely ischemic pig myocardium differs considerably from that observed in the dog. Nitroglycerin was not shown to have any beneficial effects with or without its relative hypotensive effect. More extensive study in animal models other than the dog is needed.

Animals↗
PubMed1978

Effects of nitroglycerin on cardiac function and regional blood flow distribution in conscious dogs.

The effects of intravenous infusion of nitroglycerin (NTG), 8 and 32 microgram/kg.min for 7 min, and of sublingual NTG, 1.2 mg, were examined on direct and continuous measurements of systemic, coronary, and regional hemodynamics, left ventricular (LV) dimensions, pressures, and myocardial contractility in conscious dogs. NTG induced sustained reductions in LV dimensions and transient increases in heart rate and dP/dt, and decreases in mean arterial pressure. Initially NTG increased cardiac output and flows to the coronary, mesenteric, renal, and iliac beds, while systemic and regional vascular resistances fell. Later, cardiac output, cardiac work, and mesenteric and iliac flows fell significantly below control, and significant vasoconstriction in the systemic as well as mesenteric, iliac, and coronary beds was observed at a time when LV end-diastolic dimensions were still significantly reduced. Peripheral vasoconstriction was not observed with systemic NTG in deafferented dogs or when NTG, 1 microgram/kg.min, was infused intra-arterially into the iliac bed. Thus, systemic NTG induces a biphasic response consisting of initial arteriolar vasodilation followed by vasoconstriction in the mesenteric, iliac, coronary and systemic beds, which is presumably due to longer lasting effects on preload and to secondary reflex responses to the drug.

Administration, Oral↗
PubMed1978

Effect of ventricular end-diastolic volume on vectorcardiographic potentials of the pig.

The Brody hypothesis proposes that alterations in end-diastolic blood volume will produce changes in the magnitude of cardiac electrical potentials recorded at the body surface. To test this hypothesis, several procedures that affect end-diastolic volume were applied in 28 anesthetized domestic piglets. The pig dipole moment magnitude curve is typified by two peaks, designated M2 and M3, which responded to these procedures. Doubling heart rate by electrical pacing or hemorrhage of 20 ml/kg produced reduction in M2 by 30% and 29%, respectively. M3 rose by 27% and 29%, respectively, under these two conditions. Reduction of end-diastolic volume by partial occlusion of the vena cava produced similar effects. Maneuvers increasing end-diastolic volume produced directionally opposite effects. Temporary aortic coarctation of phenylephrine injection caused an increase in M2 with no change in M3, accompanied an acute elevation of arterial pressure. Thus, the pig electrocardiogram shows changes, attributable to adjustments in end-diastolic volume, consistent with the Brody hypothesis, suggesting potentials for this technique in monitoring changes in end-diastolic volume.

Action Potentials↗
PubMed1977

Effects of low tissue temperature on peripheral vascular control mechanisms.

Influence of low temperatures on vascular effects produced adrenaline, noradrenaline and vasoconstrictor nerve stimulation was studied in the feet of ducks. Observations were made on isolated preparations as well as on intact ducks with one or both feet immersed in ice-water. Isolated preparations were perfused with physiological solution and information on changes in vascular resistance obtained by direct measurement of flow changes during perfusion at constant pressure or by measuring changes in perfusion pressure during perfusion at constant flow. In intact ducks changes in blood flow were recorded as changes in digital subcutaneous tissue temperature. The study revealed that in the duck foot a relatively large fraction of the resistance to blood flow is found in the arteries of the proximal part of the foot. During cooling of the foot the influence of vasoconstrictor nerve stimulation and low doses of adrenaline and noradrenaline on vascular resistance is gradually lost, and it is negligible at temperatures below 8 degrees C. At these low temperatures the blood vessels stay dilated and blood flow through the web seems to be determined by the digital arterial blood pressure.

Animals↗
PubMed1977

Cardiovascular effects of radioactive microsphere suspensions and Tween 80 solutions.

The cardiovascular effects of two concentrations of Tween 80 (polyoxyethylene sorbitan mono-oleate), a surface-active agent commonly used to prevent aggregation of radionuclide-labeled microspheres, were examined in conscious dogs. Two types of adverse reactions were noted. The first (Type A) consisted of reductions in cardiac dimensions as well as hypotension and tachycardia. The second (Type B) was less severe and involved only a decrease in cardiac dimensions with no change in left ventricular systolic pressure or heart rate. A 10% dextran solution with .05 +/- .02% Tween 80 injected into the left atrium caused systemic and/or cardiac alterations in all four dogs studied. Administration of a lower concentration of Tween 80 (0.01 +/- 0.005%), which was the minimum concentration necessary to prevent aggregation of microspheres, induced adverse reactions in 6 of 41 dogs studied. Subsequent administration of this concentration of Tween 80 on the same day rarely induced adverse reactions. Thus, care must be exercised in application of microsphere techniques to organ blood flow measurements when Tween 80 is used to prevent microsphere aggregation, since this surface-active agent causes profound alterations in cardiac dynamics in concentrations normally employed in experiments involving microsphere techniques.

Animals↗
PubMed1977

Effect of hematocrit on electrocardiographic potentials and dipole moment of the pig.

The Brody hypothesis posits that blood in the heart chambers enhances body surface potentials due to radially oriented excitation and diminishes those due to tangentially oriented excitation. Evidence supporting the hypothesis has been found in models and in dogs. The current study was performed in pigs (Sus scrofa), anesthetized with sodium pentobarbital, to determine whether the phenomenon could also be demonstrated in a species having a ventricular activation pattern distinctly different from that of dogs. Hematocrit was varied from normal 35.3 +/- 1.1% to as low as 19.8% by hemodilution and to as high as 68.0% by hemoconcentration. Surface potentials early in QRS increased and those late in QRS decreased in hemodilution experiments, while the reverse was true in hemoconcentration experiments. Total QRS duration was 38.0 +/- 0.8 ms. The first peak in resultant dipole moment magnitude, at 5.4 +/- 0.2 ms, was inversely related to blood resistivity with a linear regression correlation coefficient r = -0.76; the second peak, at 10.9 +/- 0.1 ms, was directly related, r = 0.52; and the third peak, at 17.5 +/- 0.2 ms, was directly related, r = 0.89. When interpreted in accordance with the Brody hypothesis, changes in body surface potentials and in resultant dipole moment were consistent with radial excitation of the apical septum, ill-defined orientation of free ventricular wall excitation, and tangential excitation of basal left ventricle and septum.

Animals↗