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Biomedical subjects

L H Michael

Publications and source records attributed to L H Michael.

103 records · Page 6Linked to original sources
PubMed1984

Cerebral blood flow and experimental intraventricular hemorrhage.

We evaluated the effects of acute hypovolemic hypotension followed by rapid, corrective blood infusion upon sequential regional cerebral blood flows (rCBF) in nine anesthetized 24-48-h-old beagle pups using the radioactive microsphere technique. After 5 min of hemorrhagic hypotension, during which time systemic arterial blood pressures were reduced 35-45%, cerebral blood flow to all regions increased by 31-42% over steady-state values. After blood reinfusion, rCBF increased by 39-88% over control values. Highest blood flows during hypovolemia were in the medulla and pons; slightly lower values were in the cerebellum, midbrain, cortex, and thalamus; and the lowest flows were in the white matter. These flows paralleled the hierarchy of flows to these regions in the steady state. Increases in blood flow during hemorrhagic hypotension were statistically significant when compared with the control values in the medulla (P less than 0.01), pons (P less than 0.01), midbrain (P less than 0.01), cerebellum (P less than 0.01), and cortex (P less than 0.01). One minute after reinfusion of the withdrawn blood volume, blood flows further increased by substantial margins in the medulla and pons; by moderate degree in the thalamus, midbrain, and cerebellum; and mildly in the cortex and white matter. Reinfusion state flow increases were significant when compared with control values in the medulla (P less than 0.01), pons (P less than 0.01), midbrain (P less than 0.01), cerebellum (P less than 0.01), cortex (P less than 0.05), and white matter (P less than 0.01). After flow values were corrected to compensate for variations in PCO2, the increases remained significant during both hypovolemia and reperfusion for medullary, thalamic, cortical, and white matter flows. Three of the nine puppies had macroscopic intraventricular hemorrhages at autopsy.

Animals↗
PubMed1983

Sodium-calcium exchange in dog heart mitochondria: effects of ischemia and verapamil.

Na+ - Ca2+ exchange was studied in two preparations of dog heart mitochondria isolated from normal and ischemic muscle following occlusion of the circumflex (CFX) coronary artery with or without prior verapamil infusion. Na+ - Ca2+ exchange in mitochondria isolated using polytron homogenization showed sigmoidal kinetics with phosphate, whereas mitochondria isolated using gentle nagarse treatment showed hyperbolic kinetics and a Vmax 60% greater than the polytron preparation. Nagarse did not alter the sigmoidal kinetics or exchange velocities of the polytron mitochondria observed with phosphate. With acetate, both preparations exhibited hyperbolic kinetics, and the sodium required for half-maximum activity was increased. Verapamil inhibited Na+ - Ca2+ exchange in both preparations with phosphate, but not with acetate. Thirty or sixty minutes of acute ischemia following CFX occlusion produced significant epicardial surface S-T elevation in the ischemic area and a decrease in myocardial segment shortening. Na+ - Ca2+ exchange of both ischemic preparations was depressed, and the kinetics of the polytron preparation changed to hyperbolic. Pretreatment of the experimental animals with verapamil (0.3 mg/kg) before 60 min of ischemia protected the exchange rates in both preparations, and the sigmoidicity of the polytron mitochondria was retained.

Animals↗
PubMed1983

Doppler measurement of myocardial thickening with a single epicardial transducer.

To eliminate the need for intramyocardial transducers in measuring regional left ventricular (LV) function we have developed a pulsed Doppler technique utilizing a single epicardial transducer. Wall thickening is evaluated by digitally integrating the velocity of myocardial layers passing through the sample volume located at a selected depth. Thickening fraction (TF) can then be estimated by dividing the systolic excursion by the sample volume depth. The Doppler method was compared with the transit-time method in three acute dogs by placing the 4-mm-diameter epicardial Doppler transducer over a 2-mm-diameter endocardial crystal tunneled through the LV wall. With the sample volume set to 1 mm less than the minimum LV thickness, simultaneous measurements of TF by the Doppler and transit-time methods showed good agreement (r = 0.95) during control, ischemia, volume overload, shock, and anoxia. In 28 chronically instrumented piglets signals were obtained for longer periods with Doppler transducers than with transit-time segment-length crystals. We conclude that the Doppler technique provides a high-fidelity wall thickening waveform and a good estimate of TF with minimal disturbance to the ventricle and that the technique is suitable for use in both acute and chronically instrumented animals.

Animals↗
PubMed1982

Comparative response of the developing canine myocardium to inotropic agents.

Developmental changes in cardiac muscle function were assessed in isolated dog ventricular muscle strips obtained from dogs of three age groups: 2 day, 4 wk, and adult. Active tension (AT) and maximum rate of contraction and relaxation (+dT/dt, -dT/dt) increased significantly with age. Total contraction time increased with age. Time to peak tension increased between 4 wk and adulthood, and relaxation time increased between 2 day and 4 wk (P less than 0.05). The degree of post-"extra stimulus" potentiation in response to a single premature extra stimulus (SPES) or to sustained paired stimulation (SPS) was similar in all age groups. However, a longer period of SPS was necessary to reach peak AT in young animals than in adults. AT, +dT/dt, -dT/dt, and (-dT/dt)/T increased significantly in all age groups in response to increasing concentrations of isoproterenol. However, while (+dT/dt)/T increased significantly in the 4-wk and adult groups, it remained unchanged from control in the 2-day group with increasing concentration of isoproterenol. The ED50 of isoproterenol was significantly greater in the 2-day and 4-wk groups than in the adult group. AT increased significantly in young muscles but not in adult muscles when additional calcium was added to the bath containing the highest concentration of isoproterenol. In adult muscles SPS produced the greatest AT but not in the 2-day group, which required increased calcium concentration as well as isoproterenol. Maturation of several membrane systems is implicated.

Aging↗
PubMed1981

Microspheres in cardiac lymph: control and ischemic states.

The cardiac lymph from conscious animals was monitored for the presence or absence of radiolabelled 15 micrometer microspheres during: 1) control periods after left atrial injection of microspheres and b) after circumflex coronary artery (CFX) occlusions (10--20 min total or less than 40 mins 50% of control flow) followed by full reperfusions. Microspheres (15 mu) numbering 7--150 were present in the lymph within 2 hrs after the occlusions; and in three experiments, the presence of a small number in the lymph on the following day implied continual release overnight. No microspheres were present in 8--48 hr lymph samples prior to occlusions. This study suggests that some microspheres escape from the intravascular space of the myocardium and are channeled into the cardiac lymphatics; this is apparent even after short-term ischemic events.

Animals↗
PubMed1980

Mitochondrial water in myocardial ischemia: investigation with nuclear magnetic resonance.

Nuclear magnetic resonance studies of mitochondria isolated from ischemic hearts after coronary vessel occlusion indicated a decrease in water proton relaxation times. This change coincided with a decrease in the hydration of the samples. It is suggested that in ischemia, changes in macromolecular hydration may be one of the first mechanisms to alter function in the mitochondria, which are vital to the energy-transducing process in heart muscle.

Animals↗
PubMed1979

Cardiac lymph flow in conscious dogs.

The cardiac lymphatic duct was cannulated in dogs and the exteriorized cannula allowed chronic collection of lymph during the awake state for as long as 3 wk. The surgical methodology and inherent difficulties in the technique are describ:d. Cardiac lymph flow ranged from 0.45--5.6 ml/h in the control state in 14 dogs. An occluding device and flow probe were placed on the circumflex coronary artery (CFX); ultrasonic segment length crystals were placed in the left ventricular free wall in 4 dogs. Occlusion of the CFX in these conscious dogs caused lymph flow to fall as great as 46% below control during the 1st half-hour. Reperfusion of the occluded vessel caused an increase in lymph flow as great as 67% above control. The effect on cardiac lymph flow was demonstrated for a few select drugs that have known effects on the cardiovascular system. Cardiac lymph flow was altered from control as follows: isoproterenol, 42 +/- 11% increase; RO 2-2985, 118 +/- 8% increase; verapamil, 101 +/- 10% increase; propranolol caused no significant change. The conscious dog with cardiac lymph vessel cannulated should provide a model to further study the complexities of cardiac metabolism and physiology without interference of anesthesia and surgical stress.

Animals↗
PubMed1975

Contraction of atrial and ventricular myocardium after treatment with ethylenediaminetetraacetic acid and glycerol.

Treatment of fiber bundles of EDTA produced high sarcolemmal permeability and eliminated the necessity of electrical stimulation of both strips of left atria (A) or left ventricular papillary muscles (P) in order to achieve activation. Subsequent Ca++-stimulated contractures developed peak tension in less time and with higher velocity in A than in P. Long term glycerination of fiber bundles, prepared from both A and P, disrupted subcellular membranes in addition to disruption of sarcolema. The bundles were then activated by addition of Ca++ and ATP, and the time course of contracture development was recorded. No difference was observed in the rate of contracture tension development from the onset to the peak tension developed between A and P. These results indicate that the major determinants of the differences in velocity and time course of tension development between atria and ventricles may reside in the coupling and uncoupling processes, rather than in sarcolemma or in the contractile proteins.

Action Potentials↗
PubMedDate not supplied

Role of early reperfusion in the induction of adhesion molecules and cytokines in previously ischemic myocardium.

Our studies in vitro demonstrate that neutrophil mediated injury of isolated cardiac myocytes requires the presence of ICAM-1 on the surface of the myocyte and CD11b/CD18 activation on the neutrophil. In post-ischemic cardiac lymph, there is rapid appearance of C5a activity during the first hours of reperfusion. Interleukin-6 activity is present throughout the first 72 h of reperfusion and is sufficient to induce ICAM-1 on the surface of the cardiac myocyte. In situ hybridization studies suggest that ICAM-1 mRNA is found in viable myocardial cells on the edge of the myocardial infarction within 1 h of reperfusion. ICAM-1 protein expression on cardiac myocytes is seen after 6 h of reperfusion, and increases thereafter. Non-ischemic tissue demonstrates no early induction of ICAM-1 mRNA or ICAM-1 protein on myocardial cells. In our most recent experiments, we have determined that reperfusion is an absolute requirement for the early induction of myocardial ICAM-1 mRNA in previously ischemic myocardial cells. To further assess this, we have cloned and sequenced a canine interleukin-6 (IL-6) cDNA. The data suggest that early induction of IL-6 mRNA is also reperfusion dependent as it could be demonstrated in the same ischemic and reperfused segments in which ICAM-1 mRNA was found. Peak expression of IL-6 mRNA occurred much earlier than that for ICAM-1 mRNA. Similar experiments were then performed with a molecular probe for interleukin-8 (IL-8). This chemokine is a potent neutrophil stimulant and has a higher degree of specificity for neutrophils than classic chemoattractants such as C5a.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMedDate not supplied

Hydralazine: effect on contraction mechanics of WKY and SHR rat heart muscle.

Chronic hydralazine treatment (2 weeks) in 22-week-old normotensive (WKY) and spontaneously hypertensive rats (SHR) significantly lowered the systolic blood pressure in both groups. Left ventricular papillary muscles from nontreated and treated WKY and SHR were placed in an isometric myography, and contractile indices monitored. Nontreated WKY and SHR were not statistically different comparing: tension, maximum contraction and relaxation rates, time to maximum tension, total contraction time, or passive and active length-tension curves. Hydralazine-treated WKY and SHR had significantly reduced tension and maximum rates of tension development and relaxation; passive length-tension characteristics were not altered. Stressing the papillary muscles with increased frequency of electrical stimulation (0.1-2 Hz) did not differentiate the various groups. Significant (p less than 0.05) alteration with isoproterenol (10(-9)-10(-5) M) occurred with the hydralazine-treated WKY, which responded with a greater increase in relaxation rate than the hydralazine-treated SHR. It is suggested that the clinically very useful drug, hydralazine, causes a distinct contractile state alteration in rat myocardium after treatment sufficient to lower SHR blood pressure to a normal range.

Animals↗