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T I Musch

Publications and source records attributed to T I Musch.

At least 55 records · Page 3Linked to original sources
PubMed1993

Non-invasive assessment of ventricular damage in rats with myocardial infarction.

OBJECTIVE: The aim was to evaluate whether two dimensional echocardiographic/Doppler (echo/Doppler) techniques could be used to detect left ventricular damage rapidly, accurately, and non-invasively in rats with a myocardial infarction. METHODS: Female Wistar rats were initially subjected to either a sham operation or surgery to induce a myocardial infarct by ligating the left main coronary artery. Following a minimum of six weeks to recover from the surgery, all rats were re-anaesthetised and cardiac and stroke indexes were determined at similar heart rates, using echo/Doppler techniques. Postmortem histological assessment of myocardial infarct size was compared with the non-invasive detection of left ventricular wall motion abnormalities, left ventricular dilatation, and the presence of a left ventricular aneurysm found in the living animal. RESULTS: Rats with myocardial infarction (n = 8) showed a 33(SEM 4)% reduction (p < 0.01) in cardiac index (due to a 33% reduction in stroke index) when compared to their non-infarcted counterparts (n = 5). In addition, a significant correlation (r = 0.84; n = 25; p < 0.01) was found between the assessment of left ventricular damage via non-invasive echo/Doppler measurements and the histological determination of infarct size. CONCLUSIONS: These results support the conclusion that two dimensional echo/Doppler techniques can be used to estimate rapidly and non-invasively the degree of left ventricular damage produced in living rats with myocardial infarction when compared to non-infarcted controls.

Animals↗
PubMed1993

Chronic exercise alters contractility and morphology of isolated rat cardiac myocytes.

Chronic exercise training elicits positive adaptations in cardiac contractile function and ventricular dimension. The potential contribution of single myocyte morphological and functional adaptations to these global responses to training was determined in this study. Left ventricular cardiac myocytes were isolated from the hearts of sedentary control (Sed) or exercise-trained (TR) rats. Training elicited an approximately 5% increase in resting myocyte length (Sed, 121.0 +/- 2.0 vs. TR, 126.7 +/- 2.0 microns; P < 0.05), whereas resting sarcomere length and midpoint cell width were unaffected. These data suggest that longitudinal myocyte growth contributes to the training-induced increase in end-diastolic dimension. Single myocytes (28 degrees C) were stimulated at 0.067 and 0.2 Hz and shortening dynamics assessed at extracellular Ca2+ concentrations ([Ca2+]o) of 0.6, 1.1, and 2.0 mM. In both groups, maximal extent of myocyte shortening (ESmax) increased as [Ca2+]o increased and decreased as contraction frequency increased. TR myocytes were more strongly influenced by the effects of [Ca2+]o and frequency. At 0.067 Hz and 2.0 mM, ESmax was greater in TR than in Sed myocytes. The magnitude of this difference decreased as [Ca2+]o was reduced. At 0.2 Hz, ESmax was similar in Sed and TR myocytes at 2.0 mM [Ca2+]o. As [Ca2+]o was reduced, ESmax decreased more rapidly in TR than in Sed myocytes; at 0.6 mM, ESmax was greater in Sed than in TR myocytes. Our data indicate that chronic exercise influences cardiac contractile function at the single myocyte level. This study also provides evidence in support of the hypothesis that chronic exercise influences myocyte Ca2+ influx and efflux pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Effects of chronic heart failure on skeletal muscle vascular transport capacity of rats.

The purpose of this study was to determine the effects of chronic heart failure (HF) on the vascular transport capacity of rat skeletal muscle. A large myocardial infarction (MI) was surgically produced in rats by ligating the left main coronary artery (n = 10). Sham operations were performed in control animals (Sham, n = 4). The vascular transport capacity of each animal's hindquarters was determined 8-9 mo post-MI to ensure that each rat was in a chronic state of left ventricular (LV) dysfunction and HF. With the use of an isolated, maximally vasodilated hindquarters preparation, we found that perfusion pressures, capillary pressures, capillary filtration coefficients, and precapillary vascular resistances were similar for the two groups under isogravimetric conditions. In contrast, postcapillary resistance was elevated (Sham, 0.9 +/- 0.2; MI, 1.5 +/- 0.2 mmHg.ml-1 x min x 100 g; P = 0.03), and flow to the hindquarters was reduced for rats in chronic HF compared with controls (Sham, 16.1 +/- 2.3; MI, 12.1 +/- 0.9 ml.min-1 x 100 g-1; P = 0.07). Vascular flow capacity (VFC) for the hindquarters was similar for control rats and rats with chronic HF across a wide range of perfusion pressures (20-60 mmHg). However, regional flow capacities were reduced in soleus and red gastrocnemius but not in white gastrocnemius muscles of rats in chronic HF compared with controls. These results suggest that the VFC of muscle comprised primarily of high oxidative fibers is selectively reduced in rats with chronic HF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Elevated diaphragmatic blood flow during submaximal exercise in rats with chronic heart failure.

The exercise blood flow response of muscles involved in respiration was determined in rats with a myocardial infarction (MI), which was produced by tying the left main coronary artery, and in rats that underwent sham operations (Sham). Arterial blood gases, acid-base parameters, and blood flow (ml/100 g of tissue) to the diaphragm, intercostals, and transverse abdominis muscles were measured during steady-state treadmill exercise (20% grade, 28 m/min). The responses of MI rats that were classified as having a small (MIS < 25%, n = 7), medium (25% < or = MIM < or = 35%, n = 8), and large (MIL > 35%, n = 7) infarct were compared with those of Sham (n = 12) rats using analysis of variance techniques. Results demonstrated that arterial PO2 and PCO2 were similar for all groups during exercise (PaO2 = 110-112 mmHg; PaCO2 = 28-29 mmHg) even though the MIM and MIL groups had developed a significant amount of pulmonary congestion, and the MIL group demonstrated indicators of severe left ventricular dysfunction. Blood flow to the diaphragm during exercise was significantly greater for the MIL group of rats, although blood flow to the intercostals and transverse abdominis muscles was similar across the different groups. Results from this study support the contention that MI rats (including rats with decompensated heart failure) will achieve the same effective alveolar ventilation during exercise as that found for Sham rats and in the process maintain arterial O2 saturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1993

Echocardiographic evaluation of size, function, and mass of normal and hypertrophied rat ventricles.

The noninvasive evaluation of cardiac structure and function in small animals would provide a means for investigators to repeatedly evaluate treatment effects at various stages of experimental protocols. In this study, commercially available echocardiographic and Doppler equipment was utilized to evaluate hypertrophied (HYP) and normal (SH) rat hearts. Surgically induced renovascular hypertension was used to produce a 35% increase in left ventricular (LV) weight in HYP relative to SH hearts. A commercially available echocardiographic system with integral Doppler capabilities and a 7.5-mHz single-crystal mechanical transducer was used to obtain parasternal long- and short-axis images of HYP and SH hearts in anesthetized animals. HYP hearts were found to have normal systolic function, as evidenced by preserved LV systolic and diastolic dimensions and volumes as well as fractional shortening and ejection fraction. HYP hearts demonstrated a 62% increase in their echocardiographically measured LV posterior wall thicknesses and a 44% increase in calculated ventricular mass. Both parameters were reliable in predicting the presence and degree of left ventricular hypertrophy. Doppler flow velocities through the aortic root and pulmonic valve did not differ between groups, again suggesting preserved LV systolic performance. These results indicate that two-dimensional echocardiography provides a useful means to noninvasively evaluate cardiac structure and function in rats.

Animals↗
PubMed1992

Skeletal muscle blood flow abnormalities in rats with a chronic myocardial infarction: rest and exercise.

The purpose of this study was to determine the regional distribution of blood flow deficit in the skeletal muscle vascular bed of rats with a chronic myocardial infarction (MI) and heart failure (HF). Accordingly, blood flow was determined (via radioactive microspheres) in rats with a small infarction (MI less than 30%) and in rats with a large (MI greater than 30%) infarction, induced by surgically ligating the left main coronary artery, and compared with rats that had received a sham operation. Results demonstrate that blood flow to the hindlimb musculature was significantly (P less than 0.05) less during a given level of treadmill exercise (20% grade and speed of 28 m/min) in the MI groups of rats compared with their sham counterparts. These differences in hindlimb blood flow were the result of blood flow deficits found in the individual muscles of the thigh and leg. Moreover, the blood flow deficits were more pronounced in the MI greater than 30% group of rats compared with the MI less than 30% group. The blood flow deficits found for the MI greater than 30% group of rats were positively correlated with the percentage of fast-twitch oxidative-glycolytic fibers and negatively correlated with the percentage of fast-twitch glycolytic fibers found in the individual muscles. Our study supports the contention that MI rats demonstrate skeletal muscle blood flow abnormalities during exercise. It appears that the degree of blood flow abnormalities produced in rats is dependent on the size of the MI and the amount of left ventricular dysfunction produced in the HF state.

Abdomen↗
PubMed1992

Training effects on the regional blood flow response to exercise in myocardial infarcted rats.

The regional blood flow (BF) response to submaximal exercise was determined for sedentary and trained myocardial infarcted (MI) rats. Training consisted of treadmill running (10% grade, 30 m/min) for 1 h/day, 5 days/wk for 12-14 wk and produced decreases in resting heart rate and increases in maximal O2 uptake and endurance capacity. BF determined at 2 and 6 min of exercise (via radiolabeled microspheres) demonstrated that trained rats maintained greater BF to organs found in the abdominal region when compared with their sedentary counterparts. BF to the total hindlimb musculature at 2 min of exercise was greater in sedentary rats when compared with their trained counterparts and was the consequence of greater BF to 10 of the 27 muscle or muscle parts investigated. At 6 min of exercise, BF to the total hindlimb musculature was similar between trained and sedentary rats, as BF in 9 of 27 muscles or muscle parts investigated decreased from 2 to 6 min of exercise for the sedentary group. In general, the BF patterns within and among the individual muscles of the hindlimb were different between the two groups. Trained rats tended to maintain greater BF to the predominantly red muscles, whereas the sedentary rats maintained greater BF to the predominantly white muscles at 6 min of exercise. In conclusion, the training-induced changes in BF found in this study are similar to those found previously for normal rats, and they demonstrate that endurance training produces changes in the regional distribution of BF during exercise in MI rats.

Abdomen↗
PubMed1992

Effects of sprint training on maximal stroke volume of rats with a chronic myocardial infarction.

The hemodynamic response to maximal exercise was determined in rats with a chronic myocardial infarction (MI) that were subjected to 6-8 wk of high-intensity sprint training (HIST) or limited exercise activity (sedentary control). Training was performed 6 days/wk and consisted of five 1-min bouts of treadmill running at work loads (15% grade, 97 m/min) in excess of the animal's maximal O2 uptake (VO2max). The left ventricular infarct size for the HIST and sedentary control rats was 35 +/- 4 and 34 +/- 3% of the total endocardial circumference, respectively. VO2max was significantly greater for MI rats subjected to the HIST paradigm than for sedentary control rats. This increase in VO2max was due to an increase in the maximal stroke volume that could be generated by the HIST rat during exercise, inasmuch as the maximal heart rate response and the ability to extract O2 from the blood were similar between the two groups of rats. Citrate synthase activities measured in the plantaris muscle of the HIST and sedentary control rats were similar. These results suggest that the increase in VO2max produced with HIST in MI rats may be linked to changes in central cardiac function, as indicated by the increase in maximal stroke volume that could be generated by the MI rat during maximal exercise conditions.

Animals↗
PubMed1991

Effects of high-intensity sprint training on skeletal muscle blood flow in rats.

The regional blood flow response (via radioactive microspheres) was determined for female rats after 6 wk of high-intensity sprint training (HIST) or limited cage activity as the animals exercised at work loads that would elicit maximal O2 uptake. Blood flow to the different organs of the abdominal region was greatly reduced during maximal exercise conditions, and the magnitude of the reduction appeared to be similar for both the HIST group of rats and their sedentary (SED) control counterparts. Of the 20 different hindlimb muscles examined in the present study, blood flow to the soleus, plantaris, gastrocnemius, flexor hallicus longus, vastus lateralis, rectus femoris, biceps femoris, and adductor magnus and brevis muscles was significantly greater (P less than 0.05) in the HIST rats during maximal exercise conditions than in the SED control rats. Correspondingly, blood flow to the total hindlimb during maximal exercise was also significantly greater in the HIST rats than in the SED control rats [240 +/- 18 vs. 192 +/- 15 (SE) ml.min-1.100 g-1]. These results support the contention that the increase in maximal cardiac output that is produced by HIST in the rat is primarily directed toward the working skeletal muscle and not toward the organs found in the abdominal region. We conclude from these experiments that HIST will produce significant adaptations in central cardiac function and skeletal muscle blood flow in the rat.

Animals↗
PubMed1991

Modulation of cardiac contractility by myosin light chain phosphorylation.

Cytosolic free [Ca2+] ([Ca2+]c) mediates primary regulation of cardiac contractility. Both the magnitude and time-course of [Ca2+]c transient that is elicited by a sarcolemmal action potential play central roles in defining the characteristics of the mechanical response that occurs during a single excitation-contraction coupling cycle. Numerous modulators of cardiac contractility, both hormonal and autoregulatory, act to influence contractile function via direct effects on various cellular processes that govern [Ca2+]c dynamics. Cardiac contractility can also be influenced by mechanisms that alter the responsiveness of the contractile element to activation by Ca2+ (see preceding paper). There is growing interest in the possibility that the phosphorylation of the P-light chain subunit of cardiac myosin by a Ca(2+)-calmodulin-dependent myosin light chain kinase may modulate cardiac muscle contractility by increasing the sensitivity of the contractile element to activation by Ca2+. The types of experimental data that have led to the development of this hypothesis and the unique aspects of cardiac P-light chain phosphate content regulation will be briefly addressed in this paper. Furthermore, several unresolved issues regarding the functional significance of cardiac P-light chain phosphorylation in intact myocardium are identified.

Animals↗
PubMed1991

Norepinephrine response to exercise of rats with a chronic myocardial infarction.

Plasma and tissue norepinephrine (NE) concentrations were determined at rest and after 45 min of swimming in rats with a surgically induced myocardial infarction (MI) and in rats having undergone a sham operation (SHAM). The MI rats had moderate-sized infarcts and demonstrated decreases in maximal O2 uptake (VO2max) that are consistent with the contention that the animals possessed a significant amount of left ventricular (LV) dysfunction and chronic heart failure (CHF). Plasma NE concentrations measured at rest were not significantly different between the SHAM and MI groups of rats, although a strong trend was found for the plasma NE concentrations to be elevated in the MI group. The plasma NE responses to 45 min of swimming at the same absolute submaximal workload were similar in the two groups of rats in light of the fact that the MI group of rats exercised at a greater percentage of their VO2max when compared with their SHAM counterparts. Exercise produced significant reductions in the NE concentrations of the diaphragm, vastus lateralis, red portion of the gastrocnemius, plantaris, and vastus intermedius muscles for both the SHAM and MI groups of rats. In addition, the NE concentrations measured in both the soleus and red portion of the gastrocnemius muscle were significantly greater in the MI rats when compared with their SHAM counterparts for both rest and exercise conditions. The results from the present study support the hypothesis that the sympathetic response to exercise is either unchanged or attenuated in MI rats that have a significant amount of LV dysfunction and CHF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Cardiac dysfunction in a rat model of chronic bacteremia.

Cardiac function was examined in vivo and in vitro in rats to determine if cardiac dysfunction could be demonstrated in a nonlethal model of infection. Bacteremic rats (n = 6) had a subcutaneous polymicrobial abscess produced via repeated inoculations of an encapsulated foreign body with Escherichia coli, Bacteroides fragilis, and Staphylococcus aureus while control rats (n = 6) had the same subcutaneous, encapsulated foreign body (an inflammatory focus) but were not inoculated with bacteria. Cardiovascular function was assessed indirectly in vivo by measuring the maximal O2 uptake during a progressive exercise test in both groups before and 14 days after the initiation of inoculations. Cardiac function was also assessed in vitro in the same rats by measuring stroke volumes generated at six different preloads with constant heart rate and afterload. Bacteremic rats had a significantly different fever curve and leukocytotic response than control rats over the 14 day period. The majority of rats that received inoculations demonstrated bacteremias, while none of the control animals had positive cultures for the inoculated organisms. Although in vivo assessment of cardiovascular function showed no evidence of dysfunction, in vitro assessment demonstrated a significant rightward shift of the Starling curve in bacteremic rats. These data suggest that LV dysfunction occurs even during nonlethal infections but may be masked in vivo by compensatory mechanisms.

Animals↗
PubMed1990

Physiologic and structural indices of vascular function in paraplegics.

In an effort to determine whether chronic physical forearm activity would increase both structural and physiologic indices of peripheral forearm vasodilation, we studied a group (N = 7) of individuals chronically performing high levels of arm work, young wheelchair-confined paraplegics, and compared them with ten young, able bodied control subjects. The index of vasodilator capacity was the flow response following the release of 10 min of arterial occlusion, the peak reactive hyperemic blood flow response (RHBF). The index of a structural effect of training on the vasculature was the brachial artery diameter (cm) derived by simultaneous measurement of velocity and forearm blood flow (area = flow.forearm volume.velocity-1). Vascular function differed significantly between the groups, with a greater RHBF (paraplegics, 53.8 +/- 3.7; controls, 38.2 +/- 1.5 ml.min-1.100 ml-1; P less than 0.05) and a larger brachial artery diameter at rest (paraplegics, 0.4 +/- 0.01 vs controls, 0.3 +/- 0.02 cm; P less than 0.05) in the paraplegics. We conclude that chronic upper extremity activity leads to an enhanced capability to vasodilate resistance vessels acutely and to a structural dilation of large conductance vessels.

Adult↗
PubMed1989

Ca2+-dependent heterometric and homeometric autoregulation in hypertrophied rat heart.

There is evidence to suggest that the alterations in cardiac function that accompany several forms of myocardial hypertrophy are due in part to desensitization of the heart to the positive inotropic effect of extracellular Ca2+ (Cae2+). In this study the heterometric and homeometric functional responsiveness of normal (SH) and hypertrophied (HYP) isolated working rat hearts was examined as a function of extracellular Ca2+ concentration [( Ca2+]e). Surgically induced renovascular hypertension was used to produce a 39% increase in left ventricular (LV) weight in HYP hearts relative to LV weights of SH hearts. The Cae2+ dependence of heterometric autoregulation was examined in SH and HYP hearts. At high left atrial filling pressures, HYP hearts were functionally less sensitive to changes in [Ca2+]e than were SH hearts; this difference appeared to be due to a preload-dependent increase in the functional sensitivity of SH hearts but not HYP hearts to changes in [Ca2+]e. In both SH and HYP hearts, a step increase in afterload resulted in a beat-by-beat increase in peak aortic outflow systolic pressure (AoP) independent of changes in LV diastolic pressure. Under our experimental conditions, the magnitude of this homeometric AoP increase (the Anrep effect) was similar in both SH and HYP hearts. The AoP increase occurred at a monoexponential rate (kHA) and was much faster in SH than in HYP hearts. Furthermore, KHA varied directly as a function of [Ca2+]e only in the SH hearts.

Animals↗
PubMed1989

Cardiovascular effects of dobutamine during exercise in dogs.

To test the hypothesis that stimulation of adrenergic receptors in the heart is maximal during maximal exercise, and to determine whether generalized stimulation of adrenergic receptors during strenuous exercise produces significant alterations in the normal regional distribution of blood flow that occurs during exercise, we evaluated the cardiovascular effects of the infusion of dobutamine (40 micrograms.kg-1.min-1) in mongrel dogs during treadmill running. During maximal exercise, the dobutamine infusion resulted in a significant (P less than 0.05) increase in heart rate. Exercise capacity, total body O2 consumption (VO2), and maximal arteriovenous O2 difference, however, each were reduced during the infusion of this drug. A concomitant reduction in maximal blood flow to locomotive skeletal muscle occurred. The infusion of dobutamine also resulted in an increase in heart rate at a strenuous level of submaximal exercise. However, unlike during maximal exercise, VO2 was unchanged. Blood flow to locomotive skeletal muscle increased, and there was a concomitant reduction in arteriovenous O2 difference. Blood flow reductions that normally occur in splanchnic circulations during strenuous and during maximal exercise were generally somewhat attenuated during the infusion of this drug. Thus, dobutamine, a sympathomimetic agent, produces significant cardiovascular effects when infused in high doses during exercise. Our results demonstrate that beta-adrenergic receptor reserve exists in the heart during maximal exercise in dogs. In addition, the peripheral responses that occur during the infusion of the drug provide additional evidence that different degrees of adrenergic receptor reserve normally appear to be present within different regional circulations during strenuous and during maximal exercise.

Animals↗
PubMed1989

Determinants of VO2max in rats after high-intensity sprint training.

The hemodynamic response to maximal exercise was determined in rats that were subjected to high-intensity sprint training (HIST) and rats that served as sedentary controls. Training consisted of five 1-min bouts of treadmill running at work loads (15% grade, 97 m/min) in excess of the animals' maximal O2 uptake (VO2max) interspersed with 90 s of rest. Training was performed 6 days/wk for 6 wk. After the training regimen, all rats were acutely instrumented with catheters in the right carotid artery and right ventricle. O2 uptakes, hemodynamic parameters, arterial and mixed venous O2 concentrations, blood gases, and acid-base status were determined at rest and during submaximal and maximal exercise. Results demonstrated that VO2max of HIST rats was significantly greater than that found for sedentary control rats. This increase in VO2max was due to an increase in maximal cardiac output (Qmax), since maximal arteriovenous O2 difference was similar between trained and sedentary rats. The increase in Qmax was due to an increase in maximal stroke volume (SVmax), because maximal heart rate in trained rats was similar to that in sedentary control rats. Citrate synthase and phosphofructokinase activities measured in the white gastrocnemius, plantaris, and soleus muscles of trained and sedentary rats were similar. These results suggest that the increase in VO2max produced with HIST in rats is strongly linked to an increase in central cardiac function as indicated by an increase in Qmax and SVmax.

Animals↗
PubMed1989

Cardiac adaptations to endurance training in rats with a chronic myocardial infarction.

The hemodynamic response to maximal exercise was determined in sedentary and trained rats with a chronic myocardial infarction (MI) produced by coronary artery ligation and in rats that underwent sham operations (SHAM). Infarct size in the MI groups of rats comprised 28-29% of the total left ventricle and resulted in both metabolic and hemodynamic changes that suggested that these animals had moderate compensated heart failure. The training regimen used in the present study produced significant increases in maximal O2 uptake (VO2max) when expressed in absolute terms (ml/min) or when normalized for body weight (ml.min-1.kg-1) and consisted of treadmill running at work loads that were equivalent to 70-80% of the animal's VO2max for a period of 60 min/day, 5 days/wk over an 8- to 10-wk interval. This training paradigm produced two major cardiocirculatory adaptations in the MI rat that had not been elicited previously when using a training paradigm of a lower intensity. First, the decrement in the maximal heart rate response to exercise (known as "chronotropic incompetence") found in the sedentary MI rat was completely reversed by endurance training. Second, the downregulation of cardiac myosin isozyme composition from the fast ATPase V1 isoform toward the slower ATPase (V2 and V3) isoforms in the MI rat was partially reversed by endurance training. These cardiac adaptations occurred without a significant increase in left ventricular pump function as an increase in maximal cardiac output (Qmax) and maximal stroke volume (SVmax) did not occur in the trained MI rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗