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Biomedical subjects

D E Mohrman

Publications and source records attributed to D E Mohrman.

At least 19 recordsLinked to original sources
PubMed2000

Decreased passive stiffness of cardiac myocytes and cardiac tissue from copper-deficient rat hearts.

Passive stiffness characteristics of isolated cardiac myocytes, papillary muscles, and aortic strips from male Holtzman rats fed a copper-deficient diet for approximately 5 wk were compared with those of rats fed a copper-adequate diet to determine whether alterations in these characteristics might accompany the well-documented cardiac hypertrophy and high incidence of ventricular rupture characteristic of copper deficiency. Stiffness of isolated cardiac myocytes was assessed from measurements of cellular dimensional changes to varied osmotic conditions. Stiffness of papillary muscles and aortic strips was determined from resting length-tension analyses and included steady-state characteristics, dynamic viscoelastic stiffness properties, and maximum tensile strength. The primary findings were that copper deficiency resulted in cardiac hypertrophy with increased cardiac myocyte size and fragility, decreased cardiac myocyte stiffness, and decreased papillary muscle passive stiffness, dynamic stiffness, and tensile strength and no alteration in aortic connective tissue passive stiffness or tensile strength. These findings suggest that a reduction of cardiac myocyte stiffness and increased cellular fragility could contribute to the reduced overall cardiac tissue stiffness and the high incidence of ventricular aneurysm observed in copper-deficient rats.

Animals↗
PubMed1998

Comparison of blood pressure responses to intra-arterial and intra-venous injections of angiotensin I, angiotensin II and bradykinin.

Because of the reported uneven vascular distribution of the enzyme, angiotensin converting enzyme (ACE), we hypothesized that the magnitude of blood pressure responses to bolus injections of angiotensin I (Ang I) and bradykinin (BK) would be dependent upon the route of administration, i.e., intra-arterial (i.a.) or intra-venous (i.v.). Anesthetized rats with cannulas in the left carotid artery and the right internal jugular vein were given bolus injections of each agent, alternating between the two cannulas. Intra-venous injections of Ang I produced transient increases in arterial pressure that were significantly greater (27 +/- 12%) and longer (7 +/- 7%) than those induced by equimolar i.a. injections within the same preparation. Intra-venous injections of BK produced transient decreases in arterial pressure that were significantly smaller (72 +/- 4%) and shorter (78 +/- 11%) than similar i.a. injections. Unexpectedly, i.v. injections of Ang II also evoked slightly larger transient increases in arterial pressure (11 +/- 4%) than similar i.a. injections. These results suggest that enzymatic alterations of Ang I and BK probably by angiotensin converting enzyme during their initial passage through the pulmonary circulation has a small but significant influence on their pressor effects.

Angiotensin I↗
PubMed1991

Adenosine receptor blockade enhances isoproterenol-induced increases in cardiac interstitial adenosine.

The failure of adenosine receptor antagonists to consistently attenuate metabolic coronary vasodilation suggests that adenosine is not a primary regulator of functional hyperemia. An alternative hypothesis, however, is that metabolic stimulation of the heart in the presence of an adenosine receptor antagonist results in enhanced interstitial levels of adenosine which then might overcome the blockade. To test this hypothesis, interstitial levels of adenosine and inosine were estimated by HPLC analysis of fluid which exudes from the epicardial surface of isolated rat hearts perfused with crystalloid solution at constant flow. Isoproterenol infusion (10 nM) produced increases in heart rate, left ventricular systolic pressure, rate of pressure development, myocardial oxygen consumption and adenosine and inosine concentrations of venous effluent and surface exudate and produced decreases in coronary vascular resistance. The presence of the adenosine receptor antagonist, 8-(4-sulfophenyl) theophylline (spT) (100 microM), in the perfusate had little or no effect upon most of the responses to isoproterenol except that it significantly enhanced the isoproterenol-induced increases in adenosine release and adenosine concentrations in the venous effluent and surface exudate. The isoproterenol-induced change in adenosine concentration per unit change in oxygen consumption was approximately 3-fold greater in the presence of spT than in its absence. This extra adenosine production may tend to overcome the competitive blocking effect of spT and help explain why agents such as spT are not always effective in blocking metabolic vasodilation.

Adenosine↗
PubMed1991

Interstitial adenosine concentration during norepinephrine infusion in isolated guinea pig hearts.

This study determined the effect of norepinephrine (NE) on cardiac interstitial fluid adenosine concentration [( ADO]isf). Isolated guinea pig hearts were perfused with a Krebs-Henseleit buffer solution. Radiolabeled albumin, sucrose, and adenosine were injected under control conditions and after 3 and 20 min of NE infusion to obtain multiple indicator dilution curves that were used to determine capillary transport parameters for adenosine. These parameters together with venous adenosine concentrations were used in a mathematical model to a calculate [ADO]isf. Capillary transport parameters were not changed significantly by NE infusion. Because of uncertainty regarding two model parameters, two sets of [ADO]isf values were calculated. One set used best-fit values obtained from indicator dilution curves, and a second set used parameters chosen to provide the highest [ADO]isf values consistent with indicator dilution curves. Venous adenosine concentrations were 1.9 +/- 0.4 nM under control conditions and 243 +/- 110 and 45 +/- 25 nM after 3 and 20 min of NE infusion, respectively. Calculated [ADO]isf was 2.6-9.4, 591-1,288, and 166-324 nM, respectively, under these same conditions. We conclude that NE infusion greatly increases [ADO]isf, and adenosine is responsible for most of the vasodilation at 3 min. The subsequent fall in venous concentration is due to a fall in [ADO]isf rather than to decreased capillary permeability. Vascular resistance remained low while [ADO]isf fell, which suggests that additional vasodilators are important during maintained NE infusion.

Adenosine↗
PubMed1990

Transcapillary adenosine transport in isolated guinea pig and rat hearts.

Transcapillary adenosine transport was studied in isolated guinea pig and rat hearts perfused with a colloid-free solution. High-performance liquid chromatography techniques were used to measure adenosine concentration of venous and interstitial (epicardial surface) fluid during steady-state perfusion with various concentrations of adenosine. A mathematical model was used to analyze these data to obtain estimates of the following parameters of transcapillary adenosine transport: PSg, permeability-surface area product for adenosine movement through interendothelial cell channels; PSecl, permeability-surface area product for adenosine movement through the luminal plasma membrane of endothelial cells; and Gec, clearance rate constant for endothelial cell metabolism and/or sequestration of adenosine. In both guinea pig and rat hearts, PSg was estimated to be less than or equal to 3 ml.min-1.g-1. Estimates of PSecl and Gec of guinea pig hearts (7.2 +/- 0.4 and 230 +/- 157 ml.min-1.g-1) were significantly less than those of rat hearts (66 +/- 11 and 2,490 +/- 1,360 ml.min-1.g-1). That PSecl is greater than PSg in both species indicates that endothelial cells represent an important pathway for transcapillary adenosine transport. That Gec is much greater than PSecl in both species implies that endothelial cells act as a sink for adenosine from surrounding areas. Our results indicate that endothelium is a stronger sink for adenosine in rat hearts than in guinea pig hearts. Inosine infusion (10(-4)M) had little effect on the estimated PSecl and Gec in guinea pig hearts but reduced these parameters several-fold in rat hearts, suggesting that different transport mechanisms for adenosine exist in endothelia of guinea pig and rat hearts.

Adenosine↗
PubMed1988

Estimates of interstitial adenosine from surface exudates of isolated rat hearts.

The adenosine concentration of exudate formed on the surface of isolated perfused rat hearts has been used to obtain estimates of interstitial values. At a constant perfusion of approximately 15 ml/min/g, exudate was collected from below ring seals that either fitted snugly (compressing seals) or that acted as wicks (wicking seals) to deflect venous effluent away from the apical surface. Steady state exudates flows obtained below each of these seals were 0.96 +/- 0.05 ml/min and 0.18 +/- 0.02 ml/min, respectively. Adenosine concentration of surface exudate and venous effluent from hearts with the compressing seal were 130 +/- 8 nM and 23 +/- 3 nM, respectively, and from those with the wicking seal were 770 +/- 93 nM and 36 +/- 9 nM, respectively. Interstitial adenosine concentration in a situation with no net filtration may be slightly higher than that achieved in the exudate from preparations with the wicking seal. Addition of exogenous adenosine to the perfusate (1.0 microM) decreased vascular resistance and automaticity of all preparations, increased the venous effluent adenosine concentration to 236 +/- 18 nM and 251 +/- 30 nM with the compressing and wicking seals, respectively, but did not significantly alter the exudate adenosine concentration with either of the seals. This finding suggests that increases in vascular adenosine may influence functional characteristics without altering interstitial levels. Perfusion with 10 microM adenosine increased adenosine concentration in both effluent and exudate in all preparations but the gradient was reversed so that effluent levels were significantly higher than exudate levels. We conclude that venous adenosine determinations significantly underestimate the interstitial adenosine concentration associated with endogenous adenosine production and significantly overestimate the interstitial levels achieved by infusion of exogenous adenosine.

Adenosine↗
PubMed1988

Adenosine handling in interstitia of cremaster muscle studied by bioassay.

We used video-microscopic techniques to study responses of rat cremaster muscle arterioles to adenosine (ADO) placed in a bathing solution in an effort to determine 1) the sensitivity of these vessels to local interstitial ADO concentration and 2) the parameters of interstitial adenosine handling. Two vessels, located at different depths (approximately 40 and 115 microns) below the surface of the tissue, were studied simultaneously. Invariably, a higher bath ADO concentration was required to induce vasodilation in the deeper vessel; the concentration required for 50% dilation response (EC50) for ADO dilation increased at an average of 1.8 +/- 0.2 log10 U/100 microns of depth into the tissue. This result was shown to be due to a standing gradient in interstitial ADO concentration. By extrapolating results to the tissue surface, we estimate that the EC50 for arteriolar dilation to local interstitial ADO is approximately 0.1 microM. The steepness of the tissue ADO gradient indicates that the rate constant for interstitial ADO loss is near 0.24/s. The gradients for nonmetabolizable adenosine analogues were less than 1/10th as steep as that for ADO itself. Qualitatively similar results were obtained from experiments on hamster cremaster muscle preparations.

2-Chloroadenosine↗
PubMed1988

Relation of blood flow to VO2, PO2, and PCO2 in dog gastrocnemius muscle.

We pump-perfused gastrocnemius-plantaris muscle preparations at constant pressure to study the relationship of muscle blood flow (Q) to muscle oxygen consumption (VO2), venous oxygen tension (PVO2), and venous carbon dioxide tension (PVCO2) during steady-state exercise at different rates. Tests were performed under four experimental conditions produced by altering the perfusate blood-gas status with a membrane lung. The consistency of the relationship of Q to other variables was evaluated by statistical analysis of fitted curves. Not one of the above listed variables had the same relationship with Q in all four of the experimental conditions we tested. However, we did find that a consistent relationship existed among Q, PVO2, and PVCO2 in our data. That relationship is well described by the equation (Q-23).[PVO2 - (0.5.PVCO2) - 3] = 105 (when Q is expressed in ml.100 g-1.min-1 and PVO2 and PVCO2 in mmHg). One interpretation of this result is that both PO2 and PCO2 are important variables in the control of blood flow in skeletal muscle the combined influence of which could account for nearly all of the hyperemia response to steady-state muscle exercise.

Animals↗
PubMed1984

Effect of aminophylline on adenosine and exercise dilation of rat cremaster arterioles.

The present study was undertaken to evaluate the role that adenosine may play in exercise vasodilation. Responses of rat cremaster muscle arterioles to either topically applied adenosine or muscle exercise were recorded via video-microscopy before and after topical administration of aminophylline (10(-4) M). In all experiments, alpha-adrenergic receptors were blocked by pretreatment with phentolamine. Under control conditions the average concentration of adenosine required to produce a 50% dilation response (ED50) was 1.9 X 10(-6) M, and the full dose-response curve spanned 2 log units from threshold to near maximum responses. Topical aminophylline increased the ED50 for adenosine dilation to 9.1 X 10(-6) M. Stepwise increases in muscle twitch rate produced a progressive arteriolar dilation, and the dilation associated with 2-Hz exercise approached the maximal dilation observed with adenosine. Topical aminophylline, however, had no effect on the arteriolar dilation response to cremaster muscle exercise. It is unlikely that our results can be explained by any influence that exercise might have on the arteriolar sensitivity to adenosine or on the efficacy of aminophylline blockade because aminophylline had no effect on the arteriolar response to even the lowest rates of exercise tested. We conclude either that adenosine does not mediate exercise dilation in rat cremaster muscle or that interstitial adenosine levels during exercise in the presence of 10(-4) M aminophylline are significantly higher (5X) than during exercise without aminophylline.

Adenosine↗
PubMed1983

Blood flow and oxygen consumption in skeletal muscle during sympathetic stimulation.

We studied the effects of physiological rates (0-4 Hz) of sympathetic stimulation on blood flow and oxygen consumption of extensor digitorum longus muscles isolated from anesthetized dogs. Observations were made with the preparation at rest and during isometric twitch exercise at 1 and 4 Hz produced by somatic nerve stimulation. Graded increases in sympathetic stimulation rate resulted in graded and sustained reductions in muscle blood flow in all cases. A given rate of sympathetic stimulation reduced muscle blood flow by nearly the same absolute amount regardless of muscle exercise rate. Consequently the curve relating muscle blood flow to muscle oxygen consumption was progressively shifted downward in a parallel fashion with graded increases in sympathetic stimulation rate. Sympathetic stimulation at 0.5 and 1 Hz reduced muscle oxygen consumption during 4-Hz exercise but failed to do so during rest or 1-Hz exercise. Thus even during heavy exercise, local metabolic mechanisms do not override sympathetic vasoconstriction sufficiently to prevent the latter from limiting muscle oxygen consumption. In addition, the functional consequences of sympathetic activation appear to be greater for heavily exercising muscle than resting muscle.

Animals↗
PubMed1982

Lack of influence of potassium or osmolality on steady-state exercise hyperemia.

Hyperkalemia, hyperosmolality, and hypoxia are known to have synergistic vasodilatory effects on resting skeletal muscle. The purpose of this study was to determine the importance of hyperkalemia and hyperosmolality in the hyperemia accompanying steady-state muscle exercise. Denervated dog gastrocnemius-plantaris muscles were perfused at constant pressure. Blood flow (Q), oxygen consumption (VO2), and venous potassium ion concentration ([K+]), osmolarity (OSM), and oxygen tension (PO2) were measured during steady-state exercise at rates between rest and 6 Hz. In control experiments the transition from rest to 6-Hz exercise resulted in large increases in VO2 and Q but modest increases in venous [K+] (+0.7 +/- 0.2 meq/l) and OSM (+6.1 +/- 1.2 mosmol/kg). Increasing venous [K+] by 2.3 meq/l by intra-arterial infusion of isotonic KCl had no steady-state effect on resting Q, nor did it alter the relationship of Q to VO2 or PO2 during exercise. Similarly, increasing venous OSM by 13 mosmol/kg by hypertonic saline infusion produced no alterations in steady-state exercise hyperemia. These findings indicate that neither local hyperkalemia nor hyperosmolality plays a significant role in sustaining the hyperemia of steady-state exercise.

Animals↗
PubMed1980

A servo-controlled roller pump for cardiovascular research.

This paper describes a servo-controlled roller pump system that can be applied to a variety of experimental situations that require either flow or pressure control. The roller pump employs a special race design that nearly eliminates the outflow pulsations inherent in conventional roller pumps. This pump simplifies servo-system design because the outflow rate is related to rotor speed by a fixed constant throughout a pump cycle. The system can control either speed or, with an appropriate feedback signal from an external transducer and preamplifier, the pressure on the output side of the pump. The time constant of the step response under speed control is less than 0.01 s, whereas that for pressure control is less than 0.2 s. System operation in the speed mode is independent of pump loading. In the pressure control mode, system operation is optimized for particular loading conditions by a single gain control. The pump can control pressure in loads ranging from a blind-ended tube through loads accepting up to 1 l/min.

Cardiovascular Physiological Phenomena↗
PubMed1977

Physiological characteristics of skeletal muscles of dogs and cats.

Our purpose was to determine if physiological characteristics of skeletal muscles of dogs and cats are related to their histochemical and biochemical characteristics. Maximum oxygen consumption (VO2max) and blood flow (Q) at VO2max were determined for in situ muscles of dogs and cats. Compared to cat muscles, dog muscles per unit mass had higher succinate oxidase activities, VO2max's, and Q's at VO2max's. There are positive relationships between Q at VO2max and VO2max and between VO2max and succinate oxidase activity. The higher VO2max's and succinate oxidase activities of dog muscles are consistent with the presence in these muscles of only slow-twitch fatique-resistant fibers and fast-twitch fatique-resistant fibers, whereas up to 50% of the fibers found in cat muscles are fast-twitch fatiqable. Capillary-to-fiber ratios are 2.40-2.97 for dog muscles compared to 2.17-2.84 for cat muscles. Thus the two- to threefold higher Q at VO2max for dog muscles compared to cat muscles is not due to a greater number of capillaries.

Animals↗
PubMed1975

Prolonged vasodilation following fatiguing exercise of dog skeletal muscle.

Prolonged vasodilation follows 20- and 60-min periods of stimulation (4 twitches/s) of dog skeletal muscle with blood flow held constant at 23 plus or minus 2 ml/100 g per min. During stimulation isometric tension development fell 61 plus or minus 3%, and we have operationally defined this as fatiguing exercise. During stimulation vasodilation was maximum. Following stimulation vascular resistance returned to control with average half-times of 6.9 plus or minus 0.6 and 5.8 plus or minus 0.4 min after 20 and 60 min of stimulation, respectively. This prolonged vascular recovery following fatiguing exercise is an order of magnitude slower than vascular recovery following less severe exercise. The pressor response to an intra-arterial bolus of angiotensin (0.5 mug) is not depressed during prolonged vasodilation. Prolonged vasodilation does not appear to be closely linked to changes in tissue oxygen consumption. In addition, the changes in resistance can be dissociated from changes in K+, osmolality, and lactate production following fatiguing exercise. We conclude that prolonged vasodilation following fatiguing exercise is caused by a metabolic vasodilator substance which is yet to be identified.

Angiotensin II↗
PubMed1975

Simultaneous counting of 85Kr in lung and myocardium during measurement of coronary blood flow.

Coronary blood flow rate (ml-min-1-100 g-1) was estimated by a) measuring pump flow into the cannulated circumflex branch of the left coronary artery and dividing by the weight of perfused myocardium and b) measuring the clearance of 85Kr following intra-arterial injection (detection with a 2-in. crystal with cylindrical collimation). Although the correlation between the two measurements was relatively high (r equals 0.90), the line best fitting the data was 85Kr flow equals 0.55 pump flow + 25.6. We tested the possibility that the discrepancy between the two methods was primarily due to the counting of 85Kr removed from myocardium and delivered to lung. Relative efficiency of lung counting versus myocardial counting was determined as well as clearance pattern of 85Kr from lung in each dog. A simple mathematical model which assumes no recirculation of 85Kr to heart allowed correction of coronary clearance curves using this information. When corrected 85Kr flow equals 1.00 pump flow + 4.1 (r equals 0.90). Thus, the major systematic cause for the discrepancy between the two measurements under the conditions of this experiment appears to be simultaneous counting of 85Kr in lung and in myocardium.

Adenosine↗