Biomedical subjects

B D Guth

Publications and source records attributed to B D Guth.

60 records · Page 4Linked to original sources

PubMed1984

Decreased systolic wall thickening in myocardium adjacent to ischemic zones in conscious swine during brief coronary artery occlusion.

The purpose of this study was to examine wall thickening in normally perfused myocardium adjacent to acutely ischemic zones. Regional wall thickening (%WT), internal minor axis diameter, and hemodynamics were monitored in nine conscious swine during temporary occlusion of the left circumflex coronary artery (LCCA). Animals were chronically instrumented with ultrasonic dimension gauges for measuring left ventricular (LV) wall thickness and minor axis, catheters in the left atrium and aorta, and a pneumatic occluder around the proximal LCCA. During a 2-minute occlusion of the LCCA, radiolabeled tracer microspheres (10 micron) were injected into the left atrium to determine regional myocardial blood flow (RMBF). Within the ischemic zone, reduction of %WT was related linearly (Y = 24.9 X -4.1, p less than 0.001) to reduced RMBF and endocardial/epicardial blood flow ratio was reduced from 1.30 +/- 0.12 (mean +/- SE) to 0.87 +/- 0.11 (p less than 0.01). In zones adjacent to the ischemic zones RMBF was unchanged by LCCA occlusion. RMBF and %WT were poorly correlated (r = 0.38) and endocardial/epicardial blood flow ratio was unchanged from preocclusion values. Therefore, myocardium adjacent to ischemic zones may have reduced thickening despite no apparent blood flow changes. We conclude that such dysfunction may be due to either mechanical tethering effects or a reduction of global LV function due to the presence of an acutely ischemic zone.

Animals↗

PubMedDate not supplied

Alpha 1-adrenergic blockade reduces exercise-induced regional myocardial ischemia in dogs.

The effect of selective alpha 1-adrenoceptor blockade on regional myocardial blood flow and contractile function during exercise-induced myocardial ischemia was determined in nine dogs having chronic single vessel coronary stenosis (ameroid constrictor). Treadmill exercise performed after beta-adrenoceptor blockade (1.0 mg/kg i.v. propranolol), to block potential prejunctional effects recently recognized with alpha-blockade, elicited severe regional myocardial ischemia with a steady-state reduction of regional systolic wall thickening of the post-stenotic myocardium from a resting value of 21.8% to 7.0%. Blood flow to the ischemic subendocardium was reduced from 0.76 to 0.36 ml/min/g (microspheres). Prazosin (80 micrograms/kg i.v.) was administered during continued running, and angiotensin II was simultaneously infused to prevent the decrease in systemic arterial pressure caused by prazosin. During the subsequent steady state, with arterial pressure matched to the pre-prazosin level, regional subendocardial blood flow improved to 0.60 ml/min/g and systolic wall thickening in the post-stenotic region increased modestly to 10.2%. No changes in blood flow to the outer portion of the post-stenotic region or to the remote control region were seen, and prazosin caused no effect on regional function in the control area, indicating effective blockade of prejunctional effects of prazosin (demonstrated in pilot studies). The finding that blockade of alpha 1-adrenoceptors resulted in improved ischemic zone subendocardial blood flow and contractile function are consistent with alpha 1-adrenoceptor-mediated reduction of blood flow to the ischemic subendocardium during exercise-induced ischemia in dogs with beta-blockade.

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

I(f) current mediates beta-adrenergic enhancement of heart rate but not contractility in vivo.

BACKGROUND: The hyper-polarization-activated "I(f)" current in the sinoatrial (SA) node participates in the spontaneous diastolic depolarization responsible for pacemaking function. Both sympathetic and parasympathetic control of heart rate is thought to involve modulation of I(f). This study tested whether beta-adrenoceptor activation of heart rate, but not contractile state, could be reduced by blockade of I(f) channels in the intact, anesthetized pig. METHODS: Both isoproterenol (ISO, 0.1 micrograms/kg/min i.v. for 5 min) and norepinephrine (NE, 0.3 micrograms/kg/min i.v. for 5 min) were used sequentially to activate beta-adrenoceptors in five metomidathydrochloride-anesthetized pigs. Left ventricular pressure and dP/dt, aortic blood pressure and cardiac output were measured. I(f) channels were then blocked selectively with 0.3 mg/kg i.v. zatebradine (ULFS49) and the test doses of ISO and NE were repeated. Following a further high dose (10 mg/kg, i.v.) of zatebradine, the test doses of ISO and NE were repeated once again. RESULTS: Before I(f) blockade, ISO and NE elicited reproducible increases in both heart rate and left ventricular dP/dt. Whereas NE caused an increase in both systolic (56%) and diastolic (53%) aortic pressure and a modest heart rate increase (22%), ISO caused a decrease in diastolic aortic pressure (-22%) and a marked increase in heart rate (81%). Low dose zatebradine reduced basal heart rate from 98 +/- 6 to 66 +/- 3 bpm, p < 0.05; cardiac output fell by 20%, stroke volume increased by 18% and total peripheral resistance was unchanged. ISO after low-dose zatebradine still elicited marked increases in heart rate (66 +/- 3 to 105 +/- 5 bpm, p < 0.05) and left ventricular dP/dt (774 +/- 94 to 3364 +/- 206 mmHg/s, p < 0.05) and reduced aortic diastolic pressure (37 +/- 2 to 33 +/- 1 mmHg, p < 0.05). NE after low-dose zatebradine increased heart rate (73 +/- 4 to 89 +/- 5 bpm, p < 0.05), left ventricular dP/dt (810 +/- 95 to 3372 +/- 196 mmHg/s, p < 0.05) and both systolic and diastolic aortic pressures. High dose zatebradine caused no further reduction in heart rate (77 +/- 4 vs 82 +/- 6 bpm, NS) but left ventricular dP/dt decreased (798 +/- 92 to 418 +/- 50 mmHg/s, p < 0.05) as did both systolic and diastolic aortic pressures. Subsequent administration of ISO had no effect on heart rate but increased left ventricular dP/dt from 418 +/- 50 to 3468 +/- 256 mmHg/s (p < 0.05) and systolic aortic pressure increased from 58 +/- 7 to 90 +/- 3 mmHg (p < 0.05). NE administered after high dose zatebradine also increased left ventricular dP/dt (580 +/- 54 to 2608 +/- 182 mmHg/s, p < 0.05) while heart rate fell (86 +/- 4 to 74 +/- 6 bpm, p < 0.05). Both systolic and diastolic aortic pressures increased substantially during the NE infusion after high dose zatebradine. CONCLUSION: Zatebradine dose-dependently inhibits beta-adrenoceptor-mediated heart rate increases while leaving beta-adrenoceptor-mediated increases in myocardial contractile state intact. This observation can be explained by a selective blockade of the hyperpolarization-activated current I(f) by low concentrations of the drug.

Adrenergic beta-Agonists↗

PubMedDate not supplied

Evaluation of parameters for the assessment of regional myocardial contractile function during asynchronous left ventricular contraction.

The primary purpose of this study was to evaluate parameters used for the measurement of regional myocardial contractile function in the setting of left ventricular (LV) asynchrony. Secondarily, we tested whether the peak negative value of left ventricular dP/dt (-dP/dt) can be used to estimate global LV end-systole during asynchrony. In seven anesthetized (Isoflurane) swine the left anterior descending coronary artery was cannulated and perfused at constant blood flow rates. To produce LV asynchrony, dobutamine (D) was infused into the perfusion system. This was repeated later during coronary hypoperfusion (HYPO) sufficient to produce regional contractile dysfunction. The amount of LV wall thickening during systole (% WT, sonomicrometry) was calculated using either -dP/dt or the closure of the aortic valve (AO, electromagnetic flow probe) for estimating the timing of global LV end-systole. % WT was compared to other parameters which are not dependent upon the timing of global LV end-systole, including the amplitude of the first harmonic of the Fourier transform (AMP) and regional myocardial work (WI) estimated form the left ventricular pressure-wall thickness relationship. A close correlation between global LV end-systole defined by the AO or -dP/dt existed during control, D or HYPO. During HYPO + D no such relationship was found (r = .22, NS), and % WT calculated using -dP/dt as an estimate of end-systole was underestimated when compared to % WT calculated by use of the AO to estimate end-systole (2.9 +/- 6.8% vs 6.3 +/- 6.6%, p less than .05). % WT, AMP, and WI showed similar results during control, D and HYPO. However, During HYPO increased the AMP from .59 +/- .23 mm to .76 +/- .32 mm and WI from 67 +/- 20 mm Hg*mm to 95 +/- 24 mm Hg*mm (p less than .05), respectively. This increase in regional myocardial function, however, was not detected by % WT (10.5 +/- 6.4% vs 6.3 +/- 6.6%). Thus, during left ventricular asynchrony, the measurement of LV -dP/dt to estimate the timing of global LV end-systole is inappropriate and can lead to inaccuracies in the measurement of regional contractile function. Parameters such as AMP or WI are advantageous since global LV end-systole does not need to be accurately defined.

Animals↗

PubMedDate not supplied

Ketone bodies maintain normal cardiac function and myocardial high energy phosphates during insulin-induced hypoglycemia in vivo.

It has been suggested that myocardial utilization of ketone bodies might cause deterioration of cardiac function. Therefore, the influence of ketonemia (mean: 1.3 and 3.3 mM) in the presence of hypoglycemia (mean: 33 mg/dl) on cardiac function, substrate utilization and myocardial high energy phosphate levels was studied in 10 mongrel dogs. Hypoglycemia alone led to a significant increase of mean aortic pressure, total peripheral resistance and myocardial oxygen consumption, but other hemodynamic parameters and regional myocardial function were not changed. Additional infusion of 3-hydroxybutyrate did not affect hemodynamic variables significantly. During both metabolic interventions in vivo phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy showed stable levels of myocardial Pi, PCr, ATP, as well as PCr/Pi (3.2-3.4) and PCr/ATP (3.0-3.2) ratios. Biochemical measurements revealed that ketonemia led to significant alterations in arterial concentrations and arterio-coronary venous differences of selected citric acid cycle intermediates, thus confirming previous reports which suggested a blockade of the 2-oxoglutarate-dehydrogenase reaction induced by ketone body oxidation. However, despite this blockade, the energy supply to the heart was not impaired as shown by normal NMR spectroscopy and cardiac performance. It is speculated that the blockade might be due to an enhanced NADH/NAD ratio.

3-Hydroxybutyric Acid↗

PubMedDate not supplied

Effect of coronary hyperperfusion on regional myocardial function and oxygen consumption of stunned myocardium in pigs.

The "Gregg phenomenon" implies that myocardial function and oxygen consumption (MVO2) increase when coronary perfusion is enhanced within or above the autoregulatory range. We have recently demonstrated that the "Gregg phenomenon" has no significance for regional myocardial function and MVO2 in anesthetized swine in situ. There is, however, some evidence that the "Gregg phenomenon" may exist within stunned myocardium. To test whether coronary hyperperfusion increases regional myocardial function and MVO2 in stunned myocardium, in six anesthetized swine the left anterior descending coronary artery (LAD) was cannulated and perfused at constant pressure (CAP) using an extracorporal circuit. The coronary vein which parallels the LAD was cannulated to allow measurement of regional MVO2 and regional systolic wall thickening (WT%) of the anterior myocardium was assessed using sonomicrometry. Blood flow (CBF) to the LAD was increased by increasing CAP within the extracorporal circuit or by intracoronary adenosine infusion (150 micrograms/min). In normal myocardium, increasing CBF from 71.4 +/- 19.7 (SD) to 156.7 +/- 48.8 ml/min/100 g by increasing CAP from 100 +/- 10 to 190 +/- 10 mm Hg or increasing CBF from 75.1 +/- 29.1 to 189.2 +/- 45.8 ml/min/100 g by intracoronary adenosine infusion did not increase WT% (34.3 +/- 12.2% vs 32.1 +/- 10.6% and 32.3 +/- 10.7% vs 30.1 +/- 13.2%, respectively). MVO2 was not changed during enhanced CAP (6.94 +/- 1.05 vs 8.10 +/- 1.08 ml/min/100 g) and during intracoronary adenosine infusion (6.67 +/- 1.45 vs 7.30 +/- 2.23 ml/min/100 g). Twenty min of hypoperfusion followed by 30 min of reperfusion depressed WT% by 47% (p less than 0.05). However, MVO2 was only decreased by 23% (NS). In the stunned myocardium, increasing CBF from 62.1 +/- 36.4 to 157.1 +/- 60.0 ml/min by increasing CAP was not associated with an increase in WT%. MVO2, however, increased from 5.14 +/- 1.07 to 8.88 +/- 1.83 ml/min/100 g (p less than 0.05). Comparable results were achieved when CBF was increased from 60.3 +/- 28.7 to 176.9 +/- 48.5 ml/min by intracoronary adenosine infusion. WT% was unaffected, while MVO2 increased from 4.69 +/- 0.92 to 9.46 +/- 3.39 ml/min/100 g (p less than 0.05). Thus, increasing coronary perfusion within or above the autoregulatory range increases MVO2 in stunned myocardium, but without a simultaneous increase in regional myocardial function.

Adenosine↗