Cardiac Oxygen Supply Research Articles

Dobutamine reverses the vasopressin-associated impairment in cardiac index and systemic oxygen supply in ovine endotoxemia

IntroductionArginine vasopressin (AVP) is increasingly used to treat sepsis-related vasodilation and to decrease catecholamine requirements. However, AVP infusion may be associated with a marked decrease in systemic blood flow and oxygen transport. The purpose of the present study was to evaluate whether dobutamine may be titrated to reverse the AVP-related decrease in cardiac index (CI) and systemic oxygen delivery index (DO2I) in an established model of ovine endotoxemia.MethodsTwenty-four adult ewes were chronically instrumented to determine cardiopulmonary hemodynamics and global oxygen transport. All ewes received a continuous endotoxin infusion that contributed to a hypotensive-hyperdynamic circulation and death of five sheep. After 16 hours of endotoxemia, the surviving ewes (n = 19; weight 35.6 ± 1.5 kg (mean ± SEM)) were randomized to receive either AVP (0.04 Umin-1) and dobutamine (n = 8) or the vehicle (normal saline; n = 6) and compared with a third group treated with AVP infusion alone (n = 5). Dobutamine infusion was started at an initial rate of 2 μg kg-1min-1 and was increased to 5 and 10 μg kg-1 min-1 after 30 and 60 minutes, respectively.ResultsAVP infusion increased mean arterial pressure (MAP) and systemic vascular resistance index at the expense of a markedly decreased CI (4.1 ± 0.5 versus 8.2 ± 0.3 l min-1 m-2), DO2I (577 ± 68 versus 1,150 ± 50 ml min-1 m-2) and mixed-venous oxygen saturation (SvO2; 54.5 ± 1.8% versus 69.4 ± 1.0%; all p < 0.001 versus control). Dobutamine dose-dependently reversed the decrease in CI (8.8 ± 0.7 l min-1 m-2 versus 4.4 ± 0.5 l min-1 m-2), DO2I (1323 ± 102 versus 633 ± 61 ml min-1 m-2) and SvO2 (72.2 ± 1.7% versus 56.5 ± 2.0%, all p < 0.001 at dobutamine 10 μg kg-1 min-1 versus AVP group) and further increased MAP.ConclusionThis study provides evidence that dobutamine is a useful agent for reversing the AVP-associated impairment in systemic blood flow and global oxygen transport.

The impact of arteriovenous fistula formation on central hemodynamic pressures in chronic renal failure patients: A prospective study

Background: The presence of an arteriovenous (AV) fistula creates permanently high cardiac output. This may cause an imbalance between available cardiac oxygen supply in response to greater demand and increased arterial stiffness. Methods: Surrogate markers of subendocardial perfusion (subendocardial viability ratio [SEVR]) and arterial stiffness (augmentation index [AIx]) can be measured noninvasively by using pulse wave analysis on the radial pulse to obtain central pressures. We prospectively followed up nine patients with chronic renal failure (CRF) undergoing creation of an AV fistula for vascular access at regular intervals over 6 months. Results: After surgery, blood pressure and heart rate remained unchanged throughout the study period. AIx stayed the same (baseline versus 6 months, 20% ± 11% versus 22% ± 15%), but there was a decrease in SEVR immediately after surgery (−9% ± 5%; P < 0.05) that persisted for at least 3 months (−14% ± 7%; P < 0.01). At 6 months, SEVR remained below baseline values in all but one patient (mean SEVR at baseline, 166% ± 22% versus 6 months, 150% ± 20%; P < 0.05; −9% ± 7%). Conclusion: Creation of an AV fistula may directly predispose patients with CRF to a risk for myocardial ischemia caused by an adverse imbalance between subendocardial oxygen supply and increased oxygen demand consequent to a greater cardiac output. © 2002 by the National Kidney Foundation, Inc.

Cardiac and hemodynamic effects of hemodialysis and ultrafiltration

Imbalance between cardiac oxygen supply and demand may trigger cardiac events in already vulnerable hemodialysis (HD) patients. We studied the effect of ultrafiltration (UF) and HD in nine chronic HD patients by continuously measuring blood volume (BV; by Critline), blood pressure (BP; by Portapres), and changes in hemodynamics (Modelflow) during isolated UF (iUF) of 500 mL in 30 minutes and subsequent HD combined with UF (HD + UF). Aortic pressure was reconstructed from finger pressure. Changes in cardiac oxygen supply were assessed by calculating the area under the aortic pressure curve during diastole (diastolic pressure time index [DPTI]). Changes in cardiac oxygen demand were assessed by calculating systolic pressure time index (SPTI). BV decreased 4.0% ± 1.8% during UF and 7.3% ± 3.3% during HD + UF (both P < 0.01). Systolic BP did not change; diastolic and mean BP increased 11 ± 7.4 and 11 ± 8.4 mm Hg during iUF, respectively (both P < 0.01), and stabilized during HD + UF. Overall pulse pressure decreased 19 ± 11.1 mm Hg (P < 0.01). Heart rate increased 13 ± 11 beats/min (P < 0.01) and systemic vascular resistance increased 59% ± 51% (P < 0.01), whereas stroke volume and cardiac output (CO) decreased by 40% ± 17% and 30% ± 13%, respectively (both P < 0.01). Both cardiac oxygen supply (DPTI) and demand (SPTI) increased during iUF, and both decreased during HD + UF. By the end of the procedure, DPTI/SPTI ratio had increased 9% ± 8% (P < 0.05). Changes in CO correlated closely to changes in BV. Despite large changes in hemodynamics during uncomplicated UF and HD, the balance between cardiac oxygen supply and demand (DPTI/SPTI ratio) did not decrease, but improved slightly.

Effects of arteriovenous fistulas on cardiac oxygen supply and demand

Arteriovenous (AV) fistulas used for hemodialysis access may affect cardiac load by increasing the preload while decreasing the afterload. In dogs, AV fistulas have also been shown to affect coronary perfusion negatively. We investigated the net effect of AV fistulas on cardiac oxygen supply and demand. Aortic pressure waves were reconstructed from finger pressure recordings obtained on the nonfistula arm using a wave-form filter. Changes in systolic, mean, and diastolic aortic pressure were calculated, together with changes in heart rate (HR), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR) during a 60-second compression of AV fistulas in 10 patients. Changes in cardiac supply and demand were estimated by calculating the area under the aortic pressure curve during diastole [diastolic pressure time index (DPTI)] and systole [systolic pressure time index (SPTI)], respectively. During fistula compression, systolic, mean and diastolic pressure increased by 4.2 +/- 4.3, 2.6 +/- 3.0, and 2.8 +/- 2.9 mm Hg (mean +/- SD, all P < 0.05). The HR decreased by 3.8 +/- 2.5 beats per minute (P < 0.01), and SV decreased 3.7 +/- 6.1% (NS). CO decreased 9.4 +/- 8.6%, and SVR increased 14.3 +/- 11.7% (both P < 0.05). The SPTI increased by 1.5 +/- 1.5 mm Hg.sec (P < 0.01), and the DPTI increased by 7.6 +/- 8.1 mm Hg.sec (14.8% increase, P < 0.05) during compression. The ratio of supply and demand (DPTI/SPTI) improved by 13.5 +/- 13.0% (P < 0.01) when the fistula was compressed. AV fistulas have a small effect on left ventricular oxygen demand, but decrease cardiac oxygen supply considerably.

Characterisation of left ventricular relaxation in the isolated guinea pig heart.

The time constant of left ventricular pressure fall, tau, has frequently been used as a measure of myocardial relaxation in the blood-perfused, ejecting heart. The aim of the present study was to characterise tau in relation to beta-adrenergic activation, coronary perfusion pressure and flow as well as cardiac oxygen supply and demand in the isolated, isovolumically beating heart. Therefore, tau was analysed from digitised left ventricular pressure data in a total of 23 guinea pig hearts perfused with saline at constant pressure (60 cmH2O). The coronary venous adenosine concentration ([ADO]) served as an index of myocardial oxygenation. Isoprenaline (0.4-3.2 nmol l-1) decreased and propranolol (3-9 mumol l-1) increased tau dose-dependently (linear regression tau vs lg([isoprenaline]), r = 0.74; tau vs. lg([propranolol]), r = 0.66, both P < 0.05). During graded reductions in cardiac oxygen supply from 96.1 +/- 12.6 (SEM) to 44.4 +/- 4.4 microliters min-1 g-1, tau was prolonged from 61.5 +/- 12.7 to 109.9 +/- 22.6 ms while left ventricular developed pressure (LVDP) decreased from 90.7 +/- 7.2 to 40.7 +/- 5.1 mmHg. In parallel, [ADO] increased from 23.7 +/- 9.1 to 58.0 +/- 19.1 pmol ml-1 (P < 0.05). Increasing oxygen supply to 165.4 +/- 32.4 microliters min-1 g-1 augmented LVDP to 102.7 +/- 7.3 mmHg but did not change tau or [ADO]. There was a dual response of tau to changes in cardiac oxygen supply or demand. As long as oxygen supply and demand matched, tau remained constant. However, when the oxygen supply was less than 100 microliters min-1 g-1, left ventricular relaxation was prolonged in parallel to the reduction in oxygen supply. In addition, a close relationship was observed between [ADO] as an indicator of myocardial oxygenation and tau (Spearman correlation, r = 0.99, P < 0.005). We conclude that the time constant of left ventricular pressure fall, tau, sensitively reflects myocardial relaxation in the isolated, isovolumically beating guinea pig heart. Moreover, in this model left ventricular relaxation is not influenced by alterations in coronary perfusion pressure or flow as long as cardiac oxygen demand is matched by an adequate supply. Rather relaxation is strictly coupled to myocardial oxygenation as reflected by coronary venous adenosine concentrations.

Optimal control system for the intra-aortic balloon pump

An optimal control system for the intra-aortic balloon pump (IABP) is presented. Control of the IABP is based on a performance index formulated to reflect a tradeoff between maximising cardiac oxygen supply and minimising cardiac oxygen consumption. In the performance index, mean diastolic pressure (MDP) was used to represent oxygen availability and peak systolic pressure (PSP) was used to represent oxygen consumption. An algorithm, implemented using an 8-bit microcomputer, changes the deflation time of the IABP to maximise this performance index by using an optimisation technique that employs both a search and an approximation. The search produces three equally spaced points which define a region that includes the maximum of the performance index. From these points, the optimum deflation time is estimated by a quadratic approximation. The algorithm has been successfully tested using performance index curves generated by computer simulations.

Computer simulation of the mechanically-assisted failing canine circulation

A model of the cardiovascular system is presented. The model includes representations of the left and right ventricles, a nonlinear multielement model of the aorta and its main branches, and lumped models of the systemic veins and the pulmonary circulation. A simulation of the intra-aortic balloon pump and representations of physiological compensatory mechanisms are also incorporated in the model. Parameters of the left ventricular model were set to simulate either the normal or failing canine circulation. Pressure and flow waveforms throughout the circulation as well as ventricular pressure and volume were calculated for the normal, failing, and assisted failing circulation. Cardiac oxygen supply and consumption were calculated from the model. They were used as direct indices of cardiac energy supply and utilization to assess the effects of cardiac assistance.

Increase in oxygen supply during experimental septic shock: the effects of dobutamine versus dopexamine

Dobutamine and dopexamine are synthetic adrenergic agents that can efficiently increase cardiac out-put and oxygen supply with little effect on arterial pressure. We compared the effects of these two drugs during experimental septic shock induced by endotoxin infusion in 12 mechanically ventilated dogs. In each animal, dobutamine and dopexamine were administered blindly in a successive and ran domized order at a dose of up to 4 μg/kg/min, while filling pressures were maintained at the baseline level by concurrent fluid administration. Dobutamine and dopexamine administration resulted in a significant and similar increase in cardiac output due to increases in stroke volume and heart rate. Because the arterial pressure increased with dobutamine and not with dopexamine, the left ventricular stroke work increased more with dobutamine and the systemic vascular resistance decreased more with dopexamine. Accordingly, dobutamine has a more pronounced inotropic action and dopexamine has a stronger vasodilating action.Dopexamine also improved arterial oxygenation, possibly by a bronchodilating effect.

Effects of transient increase in intrathoracic pressure on hemodynamic determinants of myocardial oxygen supply and demand.

Effects of transient increases in intrathoracic pressure on hemodynamic indexes of myocardial oxygen supply and demand were evaluated in 21 patients with ischemic heart disease. Left ventricular, ascending aortic, and right atrial pressures and electrocardiogram (ECG) were recorded while a Valsalva maneuver was performed during ischemia. Myocardial oxygen demand was assessed from the tension time index (TTI) and cardiac size and potential myocardial oxygen supply were assessed from a diastolic pressure time index (DPTI) and relative changes in supply/demand ratio from DPTI/TTI. During an asymptomatic interval an abrupt but small transient decrease in TTI and cardiac size occurred during phase II (p less than 0.05) of the Valsalva maneuver. DPTI did not change significantly and DPTI/TTI increased (p less than 0.05). When Valsalva maneuver was initiated during angina, 16 patients reported prompt and complete relief of angina, and left ventricular end-diastolic pressure declined following the maneuver. Relief of ischemia occurred uniformly during the latter part of straining (phase II) coincident with the peak reduction in TTI, cardiac size, and increase in DPTI/TTI. These data indicate that a transient increase in intrathoracic pressure results in a decrease in hemodynamic determinants of myocardial oxygen demand and an increase in the myocardial oxygen supply:demand ratio.

Cardiac beat frequency and oxygen supply: A comparative study

1. 1. The length of diastole in mammals varies between approx 1 s (elephant) and 38ms (shrew) which makes oxygen supply in high speed cardiac pumps in very small mammals precarious. 2. 2. High capillary density and high blood P 50, are reported in mammals with high frequency cardiac cycle. 3. 3. Both are probably insufficient when cardiac frequency is exceedingly high (shrew: 1000 min −1). 4. 4. High respiratory efficiency due to large relative mitochondrial volume per cell ( > 50%) seems to be preferential solution to maintain sufficient O 2-gradient. 5. 5. Similar strategy, i.e. high relative cardiac mitochondrial volume was reported in analogous situation in ice-fish ( Chaenocephalus aceratus) where O 2 cardiac cell supply is difficult due to the absence of hemoglobin and cardiac myoglobin.

The effect of alpha-adrenergic blockade on cardiac performance and tissue oxygen delivery during excision of pheochromocytoma.

To establish criteria for administration of the optimal dose of alpha-adrenergic receptor blocking drugs, we studied cardiac performance and tissue oxygen tension in three patients who underwent excision of pheochromocytoma. Subcutaneous oxygen tension was measured by the method of Niinikoski and Hunt. Cardiac function was assessed by thermodilution cardiac output, systemic and pulmonary arterial blood pressures, and continuous two-dimensional transesophageal echocardiography of a cross section of the left ventricle at the level of the papillary muscles. Despite large changes in cardiac output and systemic, pulmonary, and wedge pressures, intraoperative tissue oxygen tensions and ejection fractions remained normal (even at times of peak catecholamine excretion and very abnormal wedge pressures). Studies of healthy animals that received no alpha-adrenergic receptor blocking drugs showed major decrements of tissue oxygen in response to modest doses of epinephrine. We conclude that progressive administration of alpha-adrenergic receptor blocking drugs does not absolutely protect the patient from major changes in blood pressure during operation for pheochromocytoma, but that cardiac performance and oxygen supply to the tissues are unimpaired.

Factors determining the distribution and adequacy of left ventricular myocardial blood flow.

Left ventricular subendocardial necrosis and fibrosis occurs in patients whose coronary arteries are normal (1–3). In the absence of coronary artery obstruction, these changes are likely due to a discrepancy between cardiac oxygen demands and myocardial oxygen supply.