Mechanism of the Systemic, Left Ventricular, and Coronary Vascular Tolerance to a Binge of Cocaine in Conscious Dogs

Circulation ◽  
1996 ◽  
Vol 94 (3) ◽  
pp. 534-541 ◽  
Author(s):  
Richard P. Shannon ◽  
Pedro Lozano ◽  
Qing Cai ◽  
W. Thomas Manders ◽  
You-tang Shen
Keyword(s):  
Left Ventricular ◽  
Conscious Dogs

alpha-Adrenergic control of oxygen delivery to myocardium during exercise in conscious dogs

1982 ◽  
Vol 242 (5) ◽  
pp. H805-H809 ◽  
Author(s):  
G. R. Heyndrickx ◽  
P. Muylaert ◽  
J. L. Pannier
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Coronary Sinus ◽  
Oxygen Delivery ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Adrenergic Blockade ◽  
Adrenergic Control

alpha-Adrenergic control of the oxygen delivery to the myocardium during exercise was investigated in eight conscious dogs instrumented for chronic measurements of coronary blood flow, left ventricular (LV) pressure, aortic blood pressure, and heart rate and sampling of arterial and coronary sinus blood. After alpha-adrenergic receptor blockade a standard exercise load elicited a significantly greater increase in heart rate, rate of change of LV pressure (LV dP/dt), LV dP/dt/P, and coronary blood flow than was elicited in the unblocked state. In contrast to the response pattern during control exercise, there was no significant change in coronary sinus oxygen tension (PO2), myocardial arteriovenous oxygen difference, and myocardial oxygen delivery-to-oxygen consumption ratio. It is concluded that the normal relationship between myocardial oxygen supply and oxygen demand is modified during exercise after alpha-adrenergic blockade, whereby oxygen delivery is better matched to oxygen consumption. These results indicate that the increase in coronary blood flow and oxygen delivery to the myocardium during normal exercise is limited by alpha-adrenergic vasoconstriction.

Left ventricular-arterial coupling in conscious dogs

1991 ◽  
Vol 261 (1) ◽  
pp. H70-H76 ◽  
Author(s):  
W. C. Little ◽  
C. P. Cheng
Keyword(s):  
Stroke Volume ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Arterial System ◽  
Conscious Dogs ◽  
Stroke Work ◽  
Arterial Elastance ◽  
Inotropic State ◽  
End Diastolic Volume ◽  
Wide Range

We investigated the criteria for the coupling of the left ventricle (LV) and the arterial system to maximize LV stroke work (SW) and the transformation of LV pressure-volume area (PVA) to SW. We studied eight conscious dogs that were instrumented to measure LV pressure and determine LV volume from three ultrasonically determined dimensions. The LV end-systolic pressure (PES)-volume (VES) relation was determined by caval occlusion. Its slope (EES) was compared with the arterial elastance (EA) and determined as PES per stroke volume. At rest, with intact reflexes, EES/EA was 0.96 +/- 0.20 EES/EA was varied over a wide range (0.18-2.59) by the infusion of graded doses of phenylephrine and nitroprusside before and during administration of dobutamine. Maximum LV SW, at constant inotropic state and end-diastolic volume (VED), occurred when EES/EA equaled 0.99 +/- 0.15. At constant VED and contractile state, SW was within 20% of its maximum value when EES/EA was between 0.56 and 2.29. The conversion of LV PVA to SW increased as EES/EA increased. The shape of the observed relations of the SW to EES/EA and SW/PVA to EES/EA was similar to that predicted by the theoretical consideration of LV PES-VES and arterial PES-stroke volume relations. We conclude that the LV and arterial system produce maximum SW at constant VED when EES and EA are equal; however, the relation of SW to EES/EA has a broad plateau. Only when EA greatly exceeds EES does the SW fall substantially. However, the conversion of PVA to SW increases as EES/EA increases. These observations support the utility of analyzing LV-arterial coupling in the pressure-volume plane.

Contractile function of heterogeneously perfused myocardium in conscious dogs

1989 ◽  
Vol 256 (2) ◽  
pp. H352-H360 ◽  
Author(s):  
M. Nagata ◽  
M. Lavallee
Keyword(s):  
Contractile Function ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Ischemic Myocardium ◽  
Conscious Dogs ◽  
Base Line ◽  
Circumflex Coronary Artery ◽  
Ventricular Afterload ◽  
Inotropic Stimulation

The contractile function of heterogeneously perfused segments (HET) after circumflex coronary artery occlusion (CAO) was examined in conscious dogs. At 1 h after CAO, regional shortening (SH) in nonischemic segments did not change from pre-CAO base line, and regional endocardial blood flow (REBF) increased (P less than 0.05) to 1.52 +/- 0.20 from 1.06 +/- 0.08 ml.min-1.g of tissue-1. In ischemic segments, SH was replaced by paradoxical bulging, and REBF averaged 0.07 +/- 0.02 ml.min-1.g of tissue-1. In HET with one crystal of each pair in nonischemic myocardium and the other in severely ischemic myocardium, SH at 1 h after CAO was reduced (P less than 0.01) by 53.2 +/- 3.4%. REBF maps constructed with serial sections of ventricular rings containing the crystals revealed that in HET 50 +/- 5% of the myocardium was ischemic. Therefore, in the acute phase of ischemia, the reductions in SH in HET were proportional to the amount of ischemic myocardium between recording sites. In HET, SH significantly recovered (P less than 0.01) over 4 wk after CAO but remained depressed by 26.8 +/- 5.1%. In contrast, SH in ischemic segments did not improve after CAO. In HET, the effects of inotropic stimulation and changes in left ventricular afterload on SH (as percent of base line) were similar before and at 1-4 wk after CAO. Thus, in HET, the level of dysfunction is acutely determined by the amount of ischemic myocardium between recording sites. Over 4 wk after CAO, SH improved substantially in these segments, and contractile function was not adversely influenced by an inotropic stimulation or an increase in ventricular afterload.

Load-dependent left ventricular relaxation in conscious dogs

1991 ◽  
Vol 261 (3) ◽  
pp. H691-H699 ◽  
Author(s):  
M. R. Zile ◽  
W. H. Gaasch
Keyword(s):  
Time Derivative ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Balloon Inflation ◽  
Myocardial Relaxation ◽  
Time To Peak ◽  
Contraction Duration ◽  
Dicrotic Notch ◽  
Late Systole

Load-dependent relaxation was studied in eight conscious dogs by inflating an intra-aortic balloon during late systole. Initially, the balloon was inflated at the aortic dicrotic notch and deflated before the next systole; subsequently, the inflation time was moved progressively earlier in 30-ms steps. This intervention produced an abrupt increment in left ventricular (LV) systolic pressure. The contraction duration was assessed by measuring the time required for LV pressure to fall by 50% of its maximum value (P50). The rate of LV pressure decline was assessed by measuring its peak negative first time derivative (-dP/dt) and the time constant of relaxation (tau). When the balloon was inflated during late systole (50 +/- 5 ms before aortic dicrotic notch), the time to peak -dP/dt fell, P50 fell, peak -dP/dt increased, and tau was unchanged. Thus the initial rate of LV pressure decline was accelerated, and the duration of the contraction was abbreviated. These data indicated that myocardial relaxation in the intact conscious dog is load dependent. Late systolic balloon inflations were performed after treatment with propranolol, verapamil, or caffeine. During propranolol and verapamil, the rate of LV relaxation (peak -dP/dt and tau) was slowed; however, the effects of balloon inflation on LV pressure transients were qualitatively similar to that seen in the baseline state. By contrast, caffeine prevented the abbreviation in the contraction duration caused by late-systolic balloon inflation. Thus LV relaxation remained load dependent when myocardial relaxation was slowed by propranolol or verapamil; load-dependent relaxation was attenuated by caffeine, presumably due to its influence on the sarcoplasmic reticulum.

Influence of CO2 on cardiovascular response to hypoxia in conscious dogs

1980 ◽  
Vol 239 (4) ◽  
pp. H545-H545 ◽  
Author(s):  
Raymond C. Koehler ◽  
Brian W. McDonald ◽  
John A. Krasney
Keyword(s):  
Cardiovascular Response ◽  
Left Ventricular ◽  
Vagal Afferents ◽  
Conscious Dogs ◽  
Coronary Vasodilation ◽  
Circulatory Response ◽  
Wide Range ◽  
Before And After ◽  
Tension Time ◽  
Arterial Chemoreceptor

The modulating effect of CO2 on the circulatory response to hypoxia in chronically instrumented conscious dogs was examined over a wide range of arterial partial pressure of O2 [PaO2 (from 80 to 25 Torr)] during a 41-min rebreathing period at three CO2 levels: hypocapnia (from PaCO2 of 32 to 18 Torr), eucapnia (32 Torr), and mild hypercapnia (40 Torr). Eucapnic and hypercapnic hypoxic responses were also measured after sinoaortic denervation (SAD) to assess the arterial chemoreceptor and baroreceptor reflex contributions. Elevating PaCO2 attenuated the tachycardia during hypoxia and produced progressively greater systemic, renal, and splanchnic vasoconstriction before but not after SAD. Vagal block converted the rises in renal and splanchnic flows observed during hypocapnic hypoxia to declines. The increase in left ventricular dP/d tmax was not affected by varying PaCO2 either before or after SAD. Coronary flow increased an additional onefold during hypoxia when PaCO2 was elevated both before and after SAD, but the tension-time indices did not differ significantly. These results indicate that: a) cardiopulmonary vagal afferents effectively counteract chemoreflex-induced vasoconstriction during hypocapnic hypoxia; b) chemoreflex vasoconstriction predominates in the renal and splanchnic beds when PaCO2 is elevated; c) the sinoaortic reflexes restrain the heart rate, but not the contractility response to hypoxia when PaCO2 is increased; and d) the augmented coronary vasodilation produced by CO2 is probably mediated by local CO2-hypoxic interactions.

Effects of nitroglycerin on cardiac function and regional blood flow distribution in conscious dogs

1978 ◽  
Vol 234 (3) ◽  
pp. H244-H252 ◽  
Author(s):  
S. F. Vatner ◽  
M. Pagani ◽  
J. D. Rutherford ◽  
R. W. Millard ◽  
W. T. Manders
Keyword(s):  
Cardiac Output ◽  
Regional Blood Flow ◽  
Flow Distribution ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Blood Flow Distribution ◽  
Biphasic Response ◽  
Cardiac Work ◽  
Regional Hemodynamics ◽  
Arteriolar Vasodilation

The effects of intravenous infusion of nitroglycerin (NTG), 8 and 32 microgram/kg.min for 7 min, and of sublingual NTG, 1.2 mg, were examined on direct and continuous measurements of systemic, coronary, and regional hemodynamics, left ventricular (LV) dimensions, pressures, and myocardial contractility in conscious dogs. NTG induced sustained reductions in LV dimensions and transient increases in heart rate and dP/dt, and decreases in mean arterial pressure. Initially NTG increased cardiac output and flows to the coronary, mesenteric, renal, and iliac beds, while systemic and regional vascular resistances fell. Later, cardiac output, cardiac work, and mesenteric and iliac flows fell significantly below control, and significant vasoconstriction in the systemic as well as mesenteric, iliac, and coronary beds was observed at a time when LV end-diastolic dimensions were still significantly reduced. Peripheral vasoconstriction was not observed with systemic NTG in deafferented dogs or when NTG, 1 microgram/kg.min, was infused intra-arterially into the iliac bed. Thus, systemic NTG induces a biphasic response consisting of initial arteriolar vasodilation followed by vasoconstriction in the mesenteric, iliac, coronary and systemic beds, which is presumably due to longer lasting effects on preload and to secondary reflex responses to the drug.

Effects of a novel inotropic agent, BAY y 5959, in conscious dogs: comparison with dobutamine and milrinone

1997 ◽  
Vol 272 (2) ◽  
pp. H753-H759
Author(s):  
N. Sato ◽  
M. Uechi ◽  
K. Asai ◽  
T. Patrick ◽  
R. K. Kudej ◽  
...  
Keyword(s):  
Heart Rate ◽  
Mechanical Efficiency ◽  
Myocardial Contraction ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Internal Diameter ◽  
Inotropic Agents ◽  
Pressure Development ◽  
High O2 ◽  
Myocardial O2 Consumption

Traditional inotropic agents, e.g., those that increase myocardial contraction through enhanced cyclic AMP or those that increase contractility at a relatively high O2 cost are frequently not useful in the clinical setting. Accordingly, newer agents that operate through different mechanisms have been synthesized. The goal of the present study was to compare the effects of a new Ca2+ promotor, BAY y 5959, with more traditional inotropic agents, dobutamine and milrinone, in 11 conscious dogs chronically instrumented for measurement of left ventricular (LV) and arterial pressures, LV internal diameter, wall thickness, coronary blood flow, and arterial and coronary sinus O2 content. Equi-inotropic doses of BAY y 5959 (20 microg x kg(-1) x min(-1)), dobutamine (10 microg x kg(-1) x min(-1)), and milrinone (10 microg x kg(-1) x min(-1)) were selected, which increased the LV rate of pressure development in sinus rhythm by 71-78% from similar baselines. Heart rate rose with dobutamine (+24 +/- 4%) and milrinone (+23 +/- 2%) but fell with BAY y 5959 (-35 +/- 3%). Dobutamine increased myocardial O2 consumption (MV(O2)) by 88 +/- 10%. In contrast, MV(O2) increased less with BAY y 5959 (+9 +/- 3%) and milrinone (+16 +/- 5%; P < 0.05). Furthermore, mechanical efficiency was also calculated either with direct measurement of cardiac output or by pressure-volume loops. Dobutamine and milrinone did not change efficiency; however, BAY y 5959 increased efficiency by 19 +/- 5%. With the heart rate held constant, BAY y 5959 increased MV(O2) by 32 +/- 4% but still increased efficiency by 28 +/- 7%. Thus the Ca2+ promotor BAY y 5959 has unique features that might be desirable for clinical applications where inotropic support is indicated, but increased MV(O2) without enhanced mechanical efficiency is deleterious.

Regional myocardial effects of intracoronary bradykinin in conscious dogs

1997 ◽  
Vol 272 (3) ◽  
pp. H1266-H1274 ◽  
Author(s):  
R. Houel ◽  
J. Su ◽  
F. Barbe ◽  
R. Choussat ◽  
B. Crozatier ◽  
...  
Keyword(s):  
Myocardial Function ◽  
Enzyme Inhibitor ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Wall Thickening ◽  
Regional Myocardial Function ◽  
Systemic Hemodynamic ◽  
Systolic Wall Thickening ◽  
Dose Dependent

This study examined in conscious dogs, the coronary and regional myocardial effects of bradykinin (BK) administered by intracoronary route and their modulation by an angiotensin-converting enzyme inhibitor. Eleven dogs were chronically instrumented with a left ventricular (LV) micromanometer, a circumflex coronary catheter, a flow probe, and ultrasonic crystals in the LV posterior wall. In the absence of systemic hemodynamic changes, BK (0.1-10 ng/kg i.c.) produced dose-dependent increases in coronary blood flow velocity (CBFV) and in LV posterior end-diastolic wall thickness (EDWT) but produced no change in LV regional myocardial function as assessed by LV posterior systolic wall thickening. The increases in LV EDWT and CBFV were linearly correlated. The BK B2 antagonist (HOE 140) abolished the effects of BK. Intracoronary enalaprilat (0.75 mg) extended the duration of the effect of BK on CBFV without modification of peak responses and induced a further increase in LV posterior EDWT but no change in LV regional myocardial function. Thus, in conscious dogs, the vasodilator effect of intracoronary BK alone or modulated by enalaprilat is not associated with changes in LV regional myocardial function.

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