Biomedical subjects
Publications and source records attributed to A Pridjian.
A 74-yr-old man with two prior coronary bypass surgeries experienced perforation of an occluded aortocoronary vein graft during a transluminal extraction catheter (TEC) procedure for unstable angina. The perforation was successfully closed using a Palmaz 154 stent covered with a short segment of autologous antecubital vein.
Previous studies suggest that the relationship between end-diastolic volume and stroke work calculated as the area of the pressure-volume work loop is linear, afterload independent, and sensitive to the inotropic state. The correlation of myocardial oxygen consumption with this stroke work could provide an integrated measure of cardiac performance and metabolism to assess perturbations induced by ischemia or pathologic loading conditions. Fourteen canine hearts instrumented for computerized acquisition of instantaneous pressure-volume data and quantitation of myocardial oxygen consumption were studied during progressive volume infusion on right heart bypass (1.5 to 3.5 L/min in 250 ml/min increments). Data acquisition both in the control state and during continuous infusion of calcium chloride (0.03 mEq/kg/min, n = 7) to increase contractility or phenylephrine (2 micrograms/kg/min, n = 7) to alter afterload facilitated the construction of stroke work versus end-diastolic volume and myocardial oxygen consumption versus stroke work relationships by least-squares regression analysis. The cardiac mechanics assessment for this group of dogs confirmed a highly linear (mean r = 0.984) work versus preload relationship that was unaffected by changes in afterload but sensitive to increased contractility (71% increase in slope). The myocardial energetics correlation was also linear (mean r = 0.939) and demonstrated an increased oxygen utilization characteristic of the higher inotropic state produced by calcium chloride infusion (0.047 +/- 0.003 versus 0.070 +/- 0.008 ml oxygen/beat/100 gm left ventricular weight, p = 0.008). Although phenylephrine administration produced variable perturbations of myocardial oxygen consumption, the energetics relationship for this subgroup was not statistically altered by changes in afterload. The features of this cardiac energetics assessment suggest its value as a biological marker to evaluate the postischemic, hypertrophied, or failing heart.
In canine hearts supported by cardiopulmonary bypass, isovolumic peak developed pressure (PDP, mm Hg) and myocardial oxygen consumption (MVO2, ml O2 X 10(-2)/beat/100 gm left ventricular [LV] weight) were determined at 5-ml increments of LV balloon inflation before and after either 2 hours of potassium cardioplegic arrest (ischemia, N = 7) or a comparable period of normothermic perfusion without ischemia (control, N = 6). The sensitivity of MVO2 as a marker of ischemic injury was compared with preservation of both adenosine triphosphate (ATP) stores and systolic pump function. Over a physiological range of end-diastolic volumes (5 to 35 ml) and end-diastolic pressures (0 to 18 mm Hg), the Frank-Starling curves were not depressed following both cardioplegic arrest and prolonged nonischemic perfusion. Although ATP stores decreased by 26% and 22% (ischemia and control groups, respectively; not significant), these levels did not distinguish the effects of cardioplegic arrest from prolonged perfusion. At the preinterventional measurement in both groups, PDP between 50 and 200 correlated with MVO2 from 3.0 to 10.0 (r = +0.84). Following cardioplegic arrest, postischemic MVO2 increased 137 +/- 6% when measured over the PDP range of 75 to 200 mm Hg (p less than 0.01). This change was not evident at a PDP of less than 75, in the empty beating heart, or in control hearts subjected to nonischemic extracorporeal perfusion. These data suggest that increased utilization of oxygen to develop physiological pressures may be a more sensitive indicator of ischemic injury than shifts in the pressure-volume relationship or depletion of adenine nucleotide stores.
Adjuvant slow calcium channel blockade theoretically minimizes the calcium influx attendant to potassium-induced cardioplegic arrest, particularly if clinically acceptable levels of cardiac hypothermia are not maintained. The present study assessed the efficacy of diltiazem therapy in ameliorating perturbations of myocardial oxygen consumption that could be attributable to postischemic intracellular calcium accumulation. In 30 canine hearts, myocardial oxygen consumption was determined during incremental isovolumic pressure-volume loading before and 30 minutes after 2 hours of either 20 or 28 degrees C potassium cardioplegic arrest. The intracoronary perfusate in randomized hearts was modified by the addition of diltiazem, 150 micrograms/kg. Although systolic performance (as defined by peak developed pressure as compared with balloon volume curves) was unchanged after 20 degrees C ischemia, adjuvant diltiazem therapy prevented the 44 +/- 2% (p less than .01) decrease in peak developed pressure after 28 degrees C arrest. Moreover, the 39% augmentation of postischemic myocardial oxygen consumption at specific peak developed pressure following both 20 and 28 degrees C ischemia was attenuated with diltiazem only after the warmer ischemic interval. This difference was characterized by a larger (35 +/- 2 vs. 26 +/- 2%; p less than .025) decrease in postischemic oxygen extraction despite a comparable hyperemia. These data suggest that adjuvant diltiazem therapy during potassium-induced cardioplegic arrest preserves energy-efficient pump function only after warmer ischemia, thereby limiting the clinical application of this myoprotective regimen.
The direct cardiac effects of high-dose insulin (HDI) were assessed in 13 canine hearts supported by cardiopulmonary bypass. Isovolumic peak developed pressure (PDP, mmHg), coronary blood flow (CBF, ml/beat/100 g LV) and myocardial oxygen consumption (MVO2, ml O2/beat/100 g LV) were determined during incremental left ventricular balloon inflation before and after functional depression by beta-blockade (0.2 mg/kg propranolol) or 2 hours cardioplegic ischemia at 28 degrees C. The 2 regimens gave an overall functional reduction of 46 +/- 3% and 42 +/- 2%, respectively. The hearts were then challenged with an aortic root bolus of 1000 IU insulin. A glucose clamp was maintained at physiological levels. Insulin reversed the negative inotropic effect of propranolol to 80% of control function and normalized heart rate. Despite the significant amelioration of systolic function by HDI, MVO2 indexed for cardiac effort did not change. Neither systolic function nor heart rate was changed in the ischemically depressed hearts. In conclusion, HDI reverses the negative inotropic effect of beta-adrenergic receptor blockade without augmenting oxygen utilization. Apart from effects ascribable to systemic vasodilation and metabolic shifts, no direct cardiac inotropic stimulation can be expected on the post-ischemically depressed, nondiabetic myocardium unless there is a persistent negative effect of beta-blockers.
Previous studies assessing the efficacy of myoprotective regimens have compared preischemic and postischemic myocardial oxygen consumption within a limited range of cardiac performance. However, recent data suggest that ischemia-induced perturbations in myocardial energetics may occur only when the left ventricle develops physiologic pressures. Therefore, in canine hearts supported by cardiopulmonary bypass, myocardial oxygen consumption (ml oxygen X 10(-2)/beat/100 gm left ventricular weight) was determined during incremental isovolumic pressure-volume loading before and 30 minutes after 2 hours of cardioplegic arrest. The ischemic insult was graded by maintaining myocardial temperature at 12 degrees C (Group I, n = 6), 20 degrees C (Group II, n = 7), or 28 degrees C (Group III, n = 6). Postischemic Starling curves were unchanged in Groups I and II but depressed 53% in Group III hearts (p less than 0.005). In Group I, postischemic myocardial oxygen consumption at specific peak developed pressures was similar to preischemic oxygen consumption. In contrast, postischemic Group II and III hearts consumed 39% more oxygen than preischemically when peak developed pressure exceeded 75 mm Hg (p less than 0.01). Postischemic hearts demonstrated reciprocal changes in arteriovenous oxygen content difference (24%, 30%, and 34% lower than preischemic values for Groups I, II, and III, respectively) and coronary blood flow (156%, 195%, and 192% higher than preischemic values for Groups I, II, and III, respectively). Only in Group II and III hearts did the increased coronary blood flow offset the defect in oxygen extraction such that myocardial oxygen consumption was increased. These data suggest that inefficient utilization of oxygen when the heart is developing physiologic pressures is a sensitive marker for myocardial injury after crystalloid cardioplegic arrest.
To define the pertubations in myocardial oxygen consumption (MVO2) previously noted after potassium-induced arrest, MVO2 was determined in 19 canine hearts during isovolumetric pressure-volume loading before and serially after 2 hr of cardioplegic ischemia at 20 degrees C. Starling curves were initially unchanged after cardioplegic arrest, but postischemic propranolol (0.2 mg/kg) depressed peak developed pressure 36 +/- 4% and heart rate 24 +/- 1% (p less than .01, for both). MVO2 indexed per beat and for left ventricular weight at defined ranges of peak developed pressure was augmented postischemically by 40% (p less than .05) and this increased oxygen utilization persisted after attenuation of coronary hyperemia, normalization of oxygen extraction, 1 hr of reperfusion, and effective beta-adrenergic-receptor blockade. These data suggest that increased MVO2 to generate physiologic pressures is a sensitive biological marker for cardioplegic efficacy that is independent of coronary flow and oxygen uptake and is not solely attributable to increased beta-adrenergic stimulation.
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