Relation of glycosylated hemoglobin to in vivo cardiac function in response to dobutamine in spontaneously diabetic BB Wor rats

1994 ◽  
Vol 72 (7) ◽  
pp. 722-727 ◽  
Author(s):  
Tom L. Broderick ◽  
Stephen J. Kopp ◽  
June T. Daar ◽  
Fred D. Romano ◽  
Dennis J. Paulson
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
Metabolic Control ◽  
Contractile Function ◽  
Glycosylated Hemoglobin ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Insulin Dependent ◽  
Myocardial Contractile

The contribution of metabolic control to in vivo myocardial contractile function in response to β1-adrenergic stimulation was determined in the spontaneously diabetic BB Wor rat. The study involved a group of insulin-dependent BB Wor rats showing marked variations in metabolic control, assessed by the level of glycosylated hemoglobin (gHb). These diabetic BB rats were divided into moderate and severe (%gHb > 14) diabetic groups. A group of Wistar rats and diabetes-resistant BB Wor rats served as controls. In vivo myocardial contractile function was measured under basal conditions and after i.v. dobutamine infusions in anesthetized rats, using a catheter-tip pressure transducer inserted into the left ventricle. No dramatic differences in heart rate with dobutamine stimulation were observed between the moderate, severe diabetic, and diabetes-resistant groups. However, heart rate was lower in Wistar control rats compared with these groups. Systolic left ventricular pressure was depressed in severe diabetic rats compared with Wistar controls. In addition, positive dP/dt was significantly less in the severe diabetic group at the highest doses of stimulation, whereas negative dP/dt was depressed under basal conditions and remained so with increasing doses of dobutamine. In the diabetic group maximal systolic left ventricular pressure, rate–pressure product, and negative dP/dt responses to dobutamine were all inversely correlated with gHb. These results indicate that changes in metabolic control of the insulin-dependent BB diabetic rat can contribute to a depressed myocardial contractile function.Key words: glycosylated hemoglobin, cardiac function, dobutamine, BB rat.

Co-expression of skeletal and cardiac troponin T decreases mouse cardiac function

2008 ◽  
Vol 294 (1) ◽  
pp. C213-C222 ◽  
Author(s):  
Q.-Q. Huang ◽  
H. Z. Feng ◽  
J. Liu ◽  
J. Du ◽  
L. B. Stull ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Contractile Function ◽  
Troponin T ◽  
Ex Vivo ◽  
Heart Function ◽  
Left Ventricular Pressure ◽  
Experimental System ◽  
Left Ventricular ◽  
Negative Effects

In contrast to skeletal muscles that simultaneously express multiple troponin T (TnT) isoforms, normal adult human cardiac muscle contains a single isoform of cardiac TnT. To understand the significance of myocardial TnT homogeneity, we examined the effect of TnT heterogeneity on heart function. Transgenic mouse hearts overexpressing a fast skeletal muscle TnT together with the endogenous cardiac TnT was investigated in vivo and ex vivo as an experimental system of concurrent presence of two classes of TnT in the adult cardiac muscle.This model of myocardial TnT heterogeneity produced pathogenic phenotypes: echocardiograph imaging detected age-progressive reductions of cardiac function; in vivo left ventricular pressure analysis showed decreased myocardial contractility; ex vivo analysis of isolated working heart preparations confirmed an intrinsic decrease of cardiac function in the absence of neurohumoral influence. The transgenic mice also showed chronic myocardial hypertrophy and degeneration. The dominantly negative effects of introducing a fast TnT into the cardiac thin filaments to produce two classes of Ca2+ regulatory units in the adult myocardium suggest that TnT heterogeneity decreases contractile function by disrupting the synchronized action during ventricular contraction that is normally activated as an electrophysiological syncytium.

Inotropic sensitivity to beta-adrenergic stimulation in early sepsis

1988 ◽  
Vol 255 (4) ◽  
pp. H699-H703 ◽  
Author(s):  
L. W. Smith ◽  
K. H. McDonough
Keyword(s):  
Contractile Function ◽  
Plasma Catecholamines ◽  
Left Ventricular ◽  
Adrenergic Stimulation ◽  
Maximal Increase ◽  
Beta Adrenergic ◽  
Arterial Blood ◽  
Myocardial Contractile ◽  
Early Sepsis

In early sepsis, maintenance of in vivo cardiovascular performance is at least partly dependent on sympathetic support to hearts with intrinsic contractile defects. Yet prolonged sympathetic stimulation, as occurs in sepsis, would be expected to alter the heart's ability to respond to this stimulation. We have investigated myocardial inotropic sensitivity to beta-adrenergic stimulation in a model of sepsis in which animals, at the time studied, exhibited bacteremia, normal arterial blood pressure and cardiac output, elevated heart rate, and elevated plasma catecholamines. Intrinsic myocardial contractile function, as assessed by the maximal rate of left ventricular pressure development (LV dP/dtmax) in an isovolumically contracting heart preparation, was significantly depressed in septic animals. To determine whether hearts from septic animals could respond normally to beta-adrenergic stimulation, we studied inotropic response to a bolus of isoproterenol in these isolated hearts. With maximal isoproterenol stimulation, hearts from septic animals were able to attain the same dP/dtmax as were hearts from control animals. With lower levels of isoproterenol, there was also no difference in inotropic indexes between the two groups when response was expressed as a percent of the maximal increase in dP/dtmax achieved with isoproterenol. These results suggest that in early sepsis, despite intrinsic myocardial contractile dysfunction, the ability of the heart to modulate its inotropic state in response in beta-adrenergic stimulation is intact.

Hypoxic pHi and function modulation by Na+/H+ exchange and alpha-adrenoreceptor inhibition in heart in vivo

1997 ◽  
Vol 272 (6) ◽  
pp. H2664-H2670 ◽  
Author(s):  
M. A. Portman ◽  
Y. Xiao ◽  
B. G. Broers ◽  
X. H. Ning
Keyword(s):  
Cardiac Function ◽  
Contractile Function ◽  
High Energy ◽  
Left Ventricular ◽  
Resonance Spectroscopy ◽  
Cardiac Contractile Function ◽  
Significant Drop ◽  
And Function ◽  
Phi Regulation

Regulation of intracellular pH (pHi) may contribute to maintenance of cardiac contractile function during graded hypoxia in vivo. To test this hypothesis, we disturbed pHi regulation in vivo using two approaches: alpha-adrenoreceptor antagonism with phentolamine (1 mg/kg) (Phen; n = 9); and Na+/H+ exchange inhibition with HOE-642 (2 mg/kg; n = 6) before graded hypoxia in open-chest sheep. Hemodynamic parameters including left ventricular maximal pressure development (dP/dtmax) cardiac index (CI), and left ventricular power were monitored continuously and simultaneously with high-energy phosphate levels and pHi, measured with 31P nuclear magnetic resonance spectroscopy in Phen, HOE-642, and control (Con; n = 9). In subgroups (n = 6) in Con and Phen, coronary flow, myocardial oxygen consumption (MVO2), and lactate uptake were also measured. During hypoxia, the functional parameters left ventricular dP/dtmax, CI, and left ventricular power decreased significantly compared with baseline and Con values. These decreases were preceded by a significant drop (P < 0.05) in pHi from 7.10 +/- 0.04 to 6.69 +/- 0.05 in Phen and corresponded temporally to a pHi drop from 7.10 +/- 0.02 to 6.77 +/- 0.03 in HOE-642. Decreases in pHi in Phen were not preceded by decreases in cardiac function or MVO2. In contrast, cardiac function parameters increased significantly in Con, whereas no significant pHi decrease occurred (7.07 +/- 0.03 to 6.98 +/- 0.04). We conclude that these data indicate that pHi regulation can be disrupted through alpha-adrenergic antagonism or Na+/H(+)-exchange inhibition in vivo. These studies demonstrate that pHi regulation performs a role in the modulation of cardiac function during hypoxia in vivo.

Contractile function and myofibrillar ATPase activity in the exercise-trained dog heart

1977 ◽  
Vol 43 (6) ◽  
pp. 977-982 ◽  
Author(s):  
R. T. Dowell ◽  
H. L. Stone ◽  
L. A. Sordahl ◽  
G. K. Asimakis
Keyword(s):  
Heart Rate ◽  
Exercise Training ◽  
Atpase Activity ◽  
Contractile Function ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Submaximal Exercise ◽  
Treadmill Running ◽  
Myofibrillar Atpase ◽  
Myofibrillar Atpase Activity

Myocardial contractility and the enzymatic (ATPase) activity of cardiac contractile proteins were examined after exercise training using the chronically instrumented, unanesthetized dog as an experimental model. Before training, heart rate and the maximum rate of left ventricular pressure development (max dP/dt) were measured at rest and during submaximal exercise. Animals were then subjected to an 8- to 10-wk treadmill running program. Training was verified by the establishment of a 10- to 20-beat/min reduction in heart rate during submaximal exercise. After training max dP/dt was within normal limits at rest, but significantly elevated during submaximal exercise. When max dP/dt was plotted as a function of heart rate, either with the animal standing quietly on the treadmill or during submaximal exercise, a marked elevation in max dP/dt at any given heart rate was observed following training. Myofibrillar protein yield and ATPase activity values were nearly identical in left ventricles from exercise-trained and sedentary control dogs. Although exercise training by treadmill running improved contractile function in the unanesthetized dog myocardium, this response does not appear to involve alterations in myofibrillar ATPase activity.

scholarly journals In vivo selective expression of thyroid hormone receptor α1 in endothelial cells attenuates myocardial injury in experimental myocardial infarction in mice

2014 ◽  
Vol 307 (3) ◽  
pp. R340-R346 ◽  
Author(s):  
Jorge Suarez ◽  
Hong Wang ◽  
Brian T. Scott ◽  
Haiyun Ling ◽  
Ayako Makino ◽  
...  
Keyword(s):  
Heart Rate ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Thyroid Hormone Receptor ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Experimental Myocardial Infarction ◽  
Negative Consequences ◽  
Selective Expression

Ischemic heart disease (IHD) is the single most common cause of death. New approaches to enhance myocardial perfusion are needed to improve outcomes for patients with IHD. Thyroid hormones (TH) are known to increase blood flow; however, their usefulness for increasing perfusion in IHD is limited because TH accelerates heart rate, which can be detrimental. Therefore, selective activation of TH effects is desirable. We hypothesized that cell-type-specific TH receptor (TR) expression can increase TH action in the heart, while avoiding the negative consequences of TH treatment. We generated a binary transgenic (BTG) mouse that selectively expresses TRα1 in endothelial cells in a tetracycline-inducible fashion. In BTG mice, endothelial TRα1 protein expression was increased by twofold, which, in turn, increased coronary blood flow by 77%, coronary conductance by 60%, and coronary reserve by 47% compared with wild-type mice. Systemic blood pressure was decreased by 20% in BTG mice after TRα1 expression. No effects on heart rate were observed. Endothelial TRα1 expression activated AKT/endothelial nitric oxide synthase pathway and increased A2AR adenosine receptor. Furthermore, hearts from BTG mice overexpressing TRα1 that were submitted to 20 min ischemia and 20 min reperfusion showed a 20% decline in left ventricular pressure (LVP) compared with control mice where LVP was decreased by 42%. Studies using an infarction mouse model demonstrated that endothelial overexpression of TRα1 decreased infarct size by 45%. In conclusion, selective expression of TRα1 in endothelial cells protects the heart against injury after an ischemic insult and does not result in adverse cardiac or systemic effects.

Cardiac autonomic blockade in exercising dogs

1977 ◽  
Vol 42 (6) ◽  
pp. 878-883 ◽  
Author(s):  
J. M. Atkins ◽  
L. D. Horwitz
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Autonomic Control ◽  
Cardiac Denervation ◽  
Autonomic Blockade ◽  
Myocardial Contractile Force ◽  
Myocardial Contractile ◽  
Severe Exercise

Pharmacological blockade of autonomic control of the heart was studied in dogs performing mild, moderate, and severe running exercise on a level treadmill. The dogs were studied without drugs, after atropine, after propranolol, and after both atropine and propranolol. As compared with results without drugs, cardiac denervation resulted in elevated resting heart rate (+45 beats/min) but reduced heart rate during moderate (-17 beats/min) and severe exercise (-47 beats/min); no change in cardiac output at rest or during mild exercise but decreases (-23% and -25%) during moderate and severe exercise; and reduced first derivatives of left ventricular pressure at rest (-24%) and during exercise (-35, -41, and -52% for mild, moderate, and severe loads, respectively). Cardiac denervation did not alter end-diastolic left ventricular diameter but significantly increased end-systolic diameter during exercise. It is concluded that blockade of autonomic control of the heart diminishes cardiac output during exercise by reducing heart rate and myocardial contractile force but does not alter cardiac output at rest.

Cardiac function and exercise training in conscious dogs

1977 ◽  
Vol 42 (6) ◽  
pp. 824-832 ◽  
Author(s):  
H. L. Stone
Keyword(s):  
Heart Rate ◽  
Exercise Training ◽  
Cardiac Function ◽  
Heart Rate Response ◽  
Exercise Program ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Time Intervals ◽  
Similar Time

Exercise training (T) was accomplished in 21 mongrel dogs. The animals were instrumented to measure ascending aortic flow, left ventricular pressure, and left atrial pressure. They were allowed to recover for 4 wk following surgery before accomplishing a standardized submaximal test (SMT). The exercise program alternated daily between sprint and endurance training. During T, the animals were tested while lying quietly on a laboratory table as well as during the SMT. In six animals, ventricular function curves (VFC) were obtained by rapid volume loading at similar time intervals as the SMT. Heart rate increased during the SMT but was found to be reduced in the T animals by an average of 20 beats/min. The maximum derivative of left ventricular pressure (P) increased during the SMT in T animals by an average of 2,200 Torr/s above the untrained animals. The VFC was lower in T animals than untrained animals because of a reduction in heart rate response. Results indicate a reflex adaptation of the nervous system with training to improve cardiac function.

In vivo gene delivery of HSP70i by adenovirus and adeno-associated virus preserves contractile function in mouse heart following ischemia-reperfusion

2006 ◽  
Vol 291 (6) ◽  
pp. H2905-H2910 ◽  
Author(s):  
Darrell D. Belke ◽  
Bernd Gloss ◽  
John M. Hollander ◽  
Eric A. Swanson ◽  
Hervé Duplain ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Viral Vector ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Viral Gene ◽  
Mouse Heart ◽  
Adeno Associated Virus

Inducible heat shock protein 70 (HSP70i) has been shown to exert a protective effect in hearts subjected to ischemia-reperfusion. Although studied in heat-shocked animals and in transgenic mice that constitutively overexpress the protein, the therapeutic application of the protein in the form of a viral vector-mediated HSP70i expression has not been widely examined. Accordingly, we have examined the effects of HSP70i delivered in vivo to the left ventricular free wall of the heart via viral gene therapy in mice. The affect of virally mediated HSP70i expression in preserving cardiac function following ischemia-reperfusion was examined after short-term expression (5-day adenovirus mediated) and long-term expression (8-mo adeno-associated virus mediated) in mice by subjecting ex vivo Langendorff perfused hearts to a regime of ischemia-reperfusion. Both vectors were capable of increasing HSP70i expression in the heart, and neither vector had any effect on cardiac function during aerobic (preischemic) perfusion when compared with corresponding controls. In contrast, both adenovirus-mediated and adeno-associated virus-mediated expression of HSP70i improved the contractile recovery of the heart after 120 min of reperfusion following ischemia. This study demonstrates the feasibility of using both short- and long-term expression of virally mediated HSP70i as a therapeutic intervention against cardiac ischemia-reperfusion injury.

scholarly journals Positive inotropic and negative lusitropic effects of endothelin receptor agonism in vivo

2005 ◽  
Vol 289 (4) ◽  
pp. H1702-H1709 ◽  
Author(s):  
D. Konrad ◽  
A. Oldner ◽  
M. Wanecek ◽  
A. Rudehill ◽  
E. Weitzberg ◽  
...  
Keyword(s):  
Left Ventricular Pressure ◽  
Receptor Activation ◽  
Left Ventricular ◽  
Stroke Work ◽  
Ventricular Relaxation ◽  
Pressure Decay ◽  
Pressure Volume Relationship ◽  
Myocardial Contractile ◽  
Isovolumic Relaxation

The endothelin (ET) system is involved in the regulation of myocardial function in health as well as in several diseases, such as congestive heart failure, myocardial infarction, and septic myocardial depression. Conflicting results have been reported regarding the acute contractile properties of ET-1. We therefore investigated the effects of intracoronary infusions of ET-1 and of the selective ETB receptor-selective agonist sarafotoxin 6c with increasing doses in anesthetized pigs. Myocardial effects were measured through analysis of the left ventricular pressure-volume relationship. ET-1 elicited increases in the myocardial contractile status (end-systolic elastance value of 0.94 ± 0.11 to 1.48 ± 0.23 and preload recruitable stroke work value of 68.7 ± 4.7 to 83.4 ± 7.2) that appear to be mediated through ETA receptors, whereas impairment in left ventricular isovolumic relaxation (τ = 41.5 ± 1.4 to 58.1 ± 5.0 and t1/2 = 23.0 ± 0.7 to 30.9 ± 2.6, where τ is the time constant for pressure decay and t1/2 is the half-time for pressure decay) was ETB receptor dependent. In addition, intravenous administration of ET-1 impaired ventricular relaxation but had no effect on contractility. Intracoronary sarafotoxin 6c administration caused impairments in left ventricular relaxation (τ from 43.3 ± 1.8 to 54.4 ± 3.4) as well as coronary vasoconstriction. In conclusion, ET-1 elicits positive inotropic and negative lusitropic myocardial effects in a pig model, possibly resulting from ETA and ETB receptor activation, respectively.

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