Right latissimus dorsi cardiomyoplasty improves left ventricular energetics.

BACKGROUND: The mechanism by which cardiomyoplasty appears to enhance left ventricular (LV) function is not well understood. We applied the time-varying elastance model to study the effect of cardiomyoplasty on LV function, ventriculovascular coupling, and LV energetics in an acute canine model. METHODS: Right latissimus dorsi cardiomyoplasty was performed in 5 dogs. The end-systolic pressure-volume relation was generated by using brief caval occlusions. End-systolic elastance, effective arterial elastance, stroke work, internal work, total mechanical work, and stroke work efficiency (stroke work/total mechanical work) were calculated from these pressure-volume data. Myocardial oxygen consumption and overall mechanical efficiency (stroke work/myocardial oxygen consumption) were predicted using the myocardial oxygen consumption-total mechanical work relation. RESULTS: Skeletal muscle contraction significantly increased end-systolic elastance, an index of contractility. Although stroke work did not change significantly, the increase in end-systolic elastance led to a 29% decrease in total mechanical work, a 50% decrease in internal work, and an increase in stroke work efficiency from 53% to 66%. This was consistent with the observed 29% decrease in effective arterial elastance/end-systolic elastance, an indicator of ventriculovascular coupling that is related inversely to stroke work efficiency. Predicted myocardial oxygen consumption decreased by at least 22%, and predicted overall mechanical efficiency increased at a minimum from 16.1% to 18.4%. CONCLUSIONS: These results support the theory that cardiomyoplasty unloads the LV by decreasing LV volumes and increasing contractility. These effects appear to improve LV energetics by decreasing total mechanical work without significantly affecting stroke work, resulting in improved stroke work efficiency. The decrease in total mechanical work strongly suggests a decrease in myocardial oxygen consumption and an increase in overall mechanical efficiency.

New technique measures decreased transmural myocardial pressure in cardiomyoplasty.

BACKGROUND: We introduce the use of a fluid-filled balloon, interposed between myocardium and latissimus dorsi (LD), as a new technique to measure transmural myocardial pressure in an acute goat model of dynamic cardiomyoplasty. METHODS: A half-ellipsoidal balloon, composed of polychloryl vinyl layers, was sutured to the atrioventricular groove in 5 goats, thereby completely enveloping both ventricles. Left LD dynamic cardiomyoplasty was then performed, anchoring the LD to the felt sewing skirt of the balloon so that the LD completely covered the balloon. Left ventricular pressure and balloon pressure were measured with the stimulator in the 1:2 mode as balloon volume was varied. RESULTS: Average transmural myocardial pressure, defined as left ventricular pressure minus balloon pressure, decreased from 34.4 mm Hg to 15.6 mm Hg during stimulator-on beats (p < 0.05). CONCLUSION: These results support the conclusion that dynamic cardiomyoplasty unloads the left ventricle by decreasing wall stress. Furthermore, transmural myocardial pressure decreased more when balloon volume was increased, implying that the LD sarcomere length has an effect on wall stress. A balloon may therefore allow optimization of LD sarcomere length and thus assisted cardiac performance.

Recovery and viability of an acute myocardial infarct after transmyocardial laser revascularization.

OBJECTIVES: The short- and long-term effectiveness of transmyocardial laser revascularization was evaluated in the setting of an acute myocardial infarction. BACKGROUND: Theoretically, transmyocardial laser revascularization allows direct perfusion of the ischemic area as ventricular blood flows through the channels to the myocardium. METHODS: Infarcts were created by coronary occlusion in 30 sheep. Eighteen of these sheep were studied to assess short-term efficacy. The infarct was reperfused after 1 h by either removing the occlusion or by laser drilling using a high power carbon dioxide laser. The occlusions were left in place for the control group. To monitor regional recovery, percent systolic shortening was measured. To evaluate long-term effectiveness, 12 additional sheep underwent creation of an infarct. Six were treated with the laser, and six were untreated. The animals were restudied 30 days later. RESULTS: In the short-term experiment, the control and reperfusion groups exhibited no recovery of regional contractility. The laser group demonstrated improvement throughout the recovery period. There was a significant difference in the area of necrosis within the same area at risk (reperfusion group 44 +/- 6% and control group 39 +/- 5% vs. laser group 6 +/- 2%). After 30 days, none of the control animals showed evidence of contraction in the infarct, whereas the laser-treated animals did. Histologic analysis of the laser-treated infarcts revealed patent channels surrounded by viable myocardium. The control-group infarcts were necrotic and scarred. CONCLUSIONS: On the basis of both short- and long-term improved contractility, as well as diminished necrosis in the area at risk, these results indicate that transmyocardial laser revascularization may be an alternative method of treating ischemic heart disease.

Right latissimus dorsi cardiomyoplasty improves left ventricular function by increasing peak systolic elastance (Emax).

BACKGROUND: Dynamic cardiomyoplasty remains a promising but poorly understood surgical modality for selected patients with dilated cardiomyopathy. Despite encouraging clinical results, objective evidence of enhanced ventricular function using traditional indexes (cardiac output, ejection fraction, and dP/dt) has been difficult to document after cardiomyoplasty. Several investigators have suggested that cardiomyoplasty acts partly by unloading the left ventricle. These indexes all depend somewhat on loading conditions, however, and might not detect such an interaction. The time-varying elastance model provides an index of contractility, Emax, that is relatively insensitive to changes in loading conditions. We applied this model to study the effect of right latissimus dorsi cardiomyoplasty on left ventricular function in an acute canine model. METHODS AND RESULTS: Five dogs underwent acute cardiomyoplasty using untrained right latissimus dorsi muscle. Instrumentation included Millar pressure transducers in the left ventricle and aortic root, an electromagnetic flow probe around the ascending aorta, and a volume conductance catheter in the left ventricle. A cuffed nerve electrode around the thoracodorsal nerve and a right ventricular sensing lead were connected to a Medtronic Cardiomyostimulator (5 V, 30 Hz, 1:1 synchronization). Transient caval occlusions were performed with the stimulator both off and on to calculate Emax and the slope of the end-systolic pressure-volume relationship (Ees). Turning the stimulator on significantly increased peak systolic elastance (Emax) and end-systolic elastance (Ees) in all five dogs by an average of 56% and 78%, respectively (P < .05). End-diastolic volume and end-systolic volume decreased by 18% and 28%, respectively (P < .05). All other measured hemodynamic parameters, including peak left ventricular pressure, mean arterial pressure, cardiac output, stroke volume, stroke work, ejection fraction, preload-recruitable stroke work, and dP/dt, did not change significantly. CONCLUSIONS: These results show that, in this acute canine model, right latissimus dorsi cardiomyoplasty significantly improves left ventricular function while decreasing left ventricular volumes. The results are consistent with the theory that cardiomyoplasty increases contractility while unloading the ventricle by decreasing end-diastolic volume. This increase in Emax despite inconsistent changes in other indexes underlies the importance of using load-insensitive indexes of ventricular function when studying cardiomyoplasty.

Prevention of complement-induced pulmonary hypertension and improvement of right ventricular function by selective thromboxane receptor antagonism.

The effect of complement activation on the pulmonary vascular system and on right ventricular function was studied in sheep (n = 12) by injection of cobra venom factor. Animals were instrumented for measurement of pulmonary flow, mean pulmonary artery pressure, right ventricular stroke work, arterial blood gases, and systemic vascular resistance. Blood was sampled from the left atrium and pulmonary artery to measure thromboxane B2, the metabolite of thromboxane A2, by radioimmunoassay. After baseline measurements, animals were randomly assigned to receive a selective thromboxane receptor antagonist SQ30741 as a 10 mg/kg bolus with an infusion of 10 mg/kg per hour or else to receive vehicle. Cobra venom factor was then injected (30 U/kg) in all animals, and data were recorded at 15, 30, 60, 90, and 120 minutes. In control animals there was a 2.4-fold increase in mean pulmonary artery pressure and a 76% increase in right ventricular stroke work at 15 minutes from baseline (p < 0.05); these values remained elevated for 30 minutes and returned to baseline by 1 hour with no change in systemic vascular resistance. Arterial oxygenation decreased by 124% at 15 minutes and remained depressed through the experiment, but in treated animals oxygen tension remained unchanged from baseline. Thromboxane B2 increased 95% from baseline in the control group and 1.5 fold in treated animals and followed a similar time course as the functional measurements (p < 0.05). A pulmonary vascular thromboxane B2 gradient of approximately 1000 pg/ml was measured at 15 and 30 minutes in both control and treated groups. (p < 0.05) We conclude that after complement activation in this model pulmonary hypertension and decreased oxygen tension are mediated by thromboxane release from the pulmonary vascular bed. This increased afterload causes a stress on the right ventricle as demonstrated by the increased right ventricular stroke work. Selective thromboxane receptor antagonism may be a beneficial therapy for pulmonary hypertension in patients after cardiopulmonary bypass.

Prevention of CD18-mediated reperfusion injury enhances the efficacy of UW solution for 15-hr heart preservation.

University of Wisconsin solution (UW) has been demonstrated to improve donor heart preservation. During reperfusion, however, myocardial performance may still remain limited by neutrophil (PMN)-mediated injury, manifested by the "low-reflow" phenomenon and myocardial "stunning." Since PMN adhesion is an important mechanism of PMN-mediated injury, we tested whether blocking PMN adhesion molecule CD18 would enhance the efficacy of UW for 15-hr heart preservation. Rabbit hearts (n = 15) were arrested with, and preserved for 15 hr in, 4 degrees C UW. After insertion of an left ventricular (LV) balloon, hearts were heterotopically transplanted into recipients pretreated with either intravenous (i.v.) saline (vehicle, n = 8) or i.v. anti-CD18 monoclonal antibody R15.7 (anti-CD18, n = 7). After 1 hr reperfusion the slope of the peak systolic pressure-volume (P-V) relation (Emax), the exponential coefficient (beta), the volume-axis intercept (Vo) of the end-diastolic P-V relation, and the time constant of the exponential LV pressure decay after dP/dt min (tau) were measured. Blood flow was measured with microspheres from which coronary vascular resistance (CVR) was calculated. Tissue %H2O was also measured. Between groups there were no significant differences in Emax (70.5 +/- 6.1 vs 63.7 +/- 6.0 mm Hg/ml, P > 0.05), beta (3.3 +/- 0.5 vs 4.3 +/- 0.5, P > 0.05), Vo (-0.4 +/- 0.1 vs -0.4 +/- 0.2 ml, P > 0.05) or %H2O (81.3 +/- 1.1 vs 80.0 +/- 0.9, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Leukotrienes D4 and E4 produced in myocardium impair coronary flow and ventricular function after two hours of global ischaemia in rat heart.

OBJECTIVE: Leukotrienes D4 and E4 are potent coronary vasoconstrictors and myocardial depressants. The aim was to investigate the contribution of myocardial leukotrienes to impairment of coronary flow and recovery of contractile function in rat hearts subjected to 2 h of global ischaemia. METHODS: Rat hearts were mounted on a working Langendorff apparatus and perfused with oxygenated Krebs-Henseleit solution at 37 degrees C for 30 min. Hearts were then arrested with either standard potassium crystalloid cardioplegic solution (n = 6), or with cardioplegic solution containing the leukotriene D4, E4 receptor antagonist Ly171883 (n = 6). Arrested hearts were maintained at 15 degrees C for 2 h, then rewarmed to 37 degrees C during 30 min working reperfusion. Coronary effluent was analysed by radioimmunoassay for leukotriene C4, D4, E4, and F4 levels. Immediately prior to cardiac arrest, and again after 30 min reperfusion, coronary flow, and aortic outflow and pressure were measured. RESULTS: Postischaemic leukotriene levels were increased compared to preischaemic levels in both groups [pooled measurements: 133.3 (SD 136.4) v 20.7(17.8) pg.0.1 ml-1, p < 0.05]. Postischaemic coronary vascular resistance was increased by 80% in controls (p < 0.001) compared to 19% (p = NS) in treated hearts. In addition, functional recovery was significantly greater in treated hearts compared to controls [82(3)% v 53(3)% for coronary flow; 79(3)% v 50(2)% for cardiac output; 82(4)% v 54(3)% for stroke work]. CONCLUSIONS: Leukotrienes are endogenously produced by the heart, and this production is significantly increased after global ischaemia and reperfusion. Reversal of significantly increased coronary vascular resistance coupled with improved functional recovery in hearts treated with LY171883 demonstrates an important contribution of endogenously produced leukotrienes to coronary vascular impairment and functional stunning of the globally ischaemic, reperfused heart.

Cardiac-derived thromboxane A2. An initiating mediator of reperfusion injury?

After crystalloid cardioplegic arrest, cardiac-derived thromboxane A2 may be an important initiating mediator of no-reflow and hemodynamic deterioration during reperfusion because of its potent vasoactive properties. Although previous studies have already documented the increased release of cardiac thromboxane A2 after ischemia, none have studied the effects of cardiac thromboxane A2 on hemodynamics. We therefore tested the ability of cardiac thromboxane A2 to mediate deterioration of coronary flow and functional recovery during reperfusion after global ischemia. Crystalloid-perfused rat hearts that had undergone Langendorff preparation (n = 30) were subjected to 2 hours of global ischemia at 15 degrees C under cardioplegic protection with (n = 15) or without (n = 15) thromboxane A2 receptor antagonist SQ29548. In eight of 15 hearts in each group, preischemic and postischemic aortic flow, coronary flow, cardiac output, heart rate, and stroke work were determined. In the remaining seven hearts in each group, preischemic and postischemic coronary effluent levels of the stable hydrolysis product of thromboxane A2 and thromboxane B2 were determined with radioimmunoassay through the use of nonrecirculating perfusate. At the completion of the experiment, water content was determined by wet weight/dry weight calculations. In a separate group (n = 7) preischemic myocardial water content was determined. Within the group protected by cardioplegic solution alone, postischemic aortic flow, coronary flow, cardiac output, and stroke work were all significantly decreased (p < 0.05) compared with preischemic values (aortic flow, 50.8 +/- 2.7 versus 29.4 +/- 3.3 ml/min; coronary flow, 13.2 +/- 1.3 versus 8.5 +/- 1.3 ml/min; cardiac output, 64.0 +/- 3.8 versus 38.0 +/- 4.4 ml/min; stroke work, 12.5 +/- 0.7 versus 7.1 +/- 0.8 cm H2O.ml). In relation to the group with cardioplegic solution alone, postischemic aortic flow, coronary flow, cardiac output, and stroke work were all significantly greater (p < 0.05) in the group with the receptor antagonist (aortic flow: 49.5 +/- 2.4 versus 29.4 +/- 3.3 ml/min; coronary flow; 12.4 +/- 1.2 versus 8.5 +/- 1.3 ml/min; cardiac output, 62.0 +/- 2.8 versus 38.0 +/- 4.4 ml/min; stroke work, 12.6 +/- 0.8 versus 7.1 +/- 0.8 cm H2O.ml). Overall, postischemic coronary effluent thromboxane B2 levels were greater than preischemic values (105.6 +/- 12.4 versus 69.6 +/- 9.8, p < 0.05) and treatment with the receptor antagonist did not significantly affect postischemic thromboxane B2 levels (92.0 +/- 7.3 versus 82.3 +/- 15.5, p = not significant). Neither ischemia nor treatment with the receptor antagonist significantly affected heart rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Myocardial stunning and reperfusion injury in cardiac surgery.

This article reviews the evidence that myocardial stunning during surgical reperfusion after coronary revascularization or heart transplantation is not strictly due to myocardial injury sustained during ischemia, but results from pathophysiological events triggered by reperfusion (reperfusion injury). In sheep, left ventricular (LV) dP/dt and stroke work were reduced up to 50%, and 60% to 70% necrosis was observed in the area at risk during 3 hours reperfusion following coronary occlusion and cardioplegic arrest on bypass. Reperfusion with leukocyte depleted blood, or pharmacological blockade of either thromboxane or leukotriene receptors, provided significant improvements in LV function and myocardial blood flow, with a 40% to 50% reduction in necrosis. Similar results have been obtained using animal heart subjected to 2 to 3 hours arrest at either 4 degrees C or 15 degrees C, simulating cardiac preservation and reperfusion after transplantation. Diastolic pressure was significantly elevated, and increases in the time constant for relaxation of LV pressure and coronary vascular resistance were noted. These indices of myocardial stunning were reversed after blocking neutrophil-endothelial cell interaction with monoclonal antibodies against CD18 or ICAM-1 receptors, and significant improvements were also obtained after either thromboxane or leukotriene receptor blockade. We conclude that immediate postoperative myocardial stunning results largely from reperfusion injury that occurs due to an acute inflammatory response to ischemia and reperfusion, and that stunning can be largely reversed with appropriate pharmacological intervention.

Thromboxane A2 mediates reperfusion injury after heart preservation.

To assess the role of the eicosanoid thromboxane A2, a potent vasoconstrictor and platelet activator, in reperfusion injury after heart preservation, donor rats (n = 18) were anesthetized, and their hearts were rapidly excised, arrested with cardioplegic solution, and fitted with a left ventricular balloon. Seven hearts were subjected to 45 minutes of ischemia at 15 degrees C, simulating implantation, (group 1) during which the carotid and jugular vessels of support rats were cannulated for ex vivo blood reperfusion. Remaining hearts were preserved in 4 degrees C saline solution for 3 hours followed by 45 minutes at 15 degrees C (group 2, n = 11). Before reperfusion of group 2 hearts, support rats received either vehicle (group 2a, n = 6) or thromboxane A2 receptor antagonist SQ29548 (0.2 mg/kg) (group 2b, n = 5). After 1 hour of reperfusion, left ventricular peak-systolic pressure and end-diastolic pressure were measured in all hearts at incremental ventricular volumes. The slope of the peak-systolic pressure-volume relation and the volume-axis intercept of the end-diastolic pressure-volume relation were also measured. No significant differences were noted in mean peak-systolic pressure, at any left ventricular volume, nor slope of the peak-systolic pressure-volume relation between groups, indicating that neither preservation nor SQ29548 treatment affected systolic contractile performance in this model. Through all left ventricular volume, however, end-diastolic pressure was significantly lower (p < 0.05) in group 2b compared to group 2a, and overall did not differ significantly from group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Complete prevention of myocardial stunning, contracture, low-reflow, and edema after heart transplantation by blocking neutrophil adhesion molecules during reperfusion.

This study tested the hypothesis that preventing neutrophil adhesion during reperfusion, by blocking either the neutrophil membrane CD18 integrin complex or its endothelial and myocyte ligand, intercellular adhesion molecule-1 (ICAM-1), would reduce myocardial inflammation and edema and improve reflow and ventricular function after heart preservation and transplantation. After cardioplegia and insertion of a left ventricular balloon, rabbit hearts were heterotopically transplanted into recipient rabbits either immediately (immediate, n = 12) or after preservation in 4 degrees C saline (3 hours of ischemia, n = 33). Forty-five minutes before reperfusion, recipients of preserved hearts received intravenous infusions of either saline (vehicle, n = 13), anti-CD18 monoclonal antibody (Mab) R15.7 (2 mg/kg) (anti-CD18, n = 10), or anti-ICAM-1 Mab R1.1 (2 mg/kg) (anti-ICAM, n = 10). During 3 hours of reperfusion the slope of the peak-systolic pressure-volume relation and its volume-axis intercept, the exponential elastic coefficient of the end-diastolic pressure-volume relation, the unstressed ventricular volume, and the time constant of the exponential left ventricular pressure decay after dP/dtmin were serially measured. Myocardial blood flow was measured with microspheres from which coronary vascular resistance was calculated. After explanation, the degree of myocardial inflammation, estimated by tissue neutrophil sequestration (myeloperoxidase assay) and myocardial water content were determined. Within each group no significant differences in measurements made at 1, 2, and 3 hours of reperfusion were noted. Compared with the immediate transplantation group, the vehicle group demonstrated a significant increase in myeloperoxidase activity (3380 +/- 456 versus 1712 +/- 552 microU/gm, p < 0.05), coronary vascular resistance (115.5 +/- 13.4 versus 70.5 +/- 10.6 U/gm, p < 0.05), and myocardial water content (79.8% +/- 0.4% versus 75.6% +/- 1.3%, p < 0.05), a significant decrease in unstressed ventricular volume (a leftward shift in the end-diastolic pressure-volume relation) (-0.49 +/- 0.24 versus 0.28 +/- 0.21 ml, p < 0.05), and a marked prolongation in exponential left ventricular pressure delay after dP/dtmin (156.64 +/- 3.81 versus 37.25 +/- 3.34 msec, p < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Bench coronary angiography: a potentially useful method to assess coronary artery disease in the older donor heart without catheterization laboratory angiography.

To assess the diagnostic accuracy of ex vivo coronary artery arteriography, 12 sheep hearts were harvested, after random multiple coronary occlusions were created. The hearts were radiographed either in the flat (n = 6) or upright suspended (n = 6) position with the aorta cross-clamped. The aortic root was cannulated with an 18-gauge needle and flushed with cold normal saline solution. Five milliliters of iodinated contrast media was injected under constant hand pressure, and angiographic views were taken with a conventional, portable x-ray machine. The aortic root was then immediately flushed with normal saline solution under constant pressure to minimize contrast contact with the vascular endothelium. Total elapsed time including film development was 7 to 10 minutes. In hearts that were radiographed lying flat, a ventriculogram was obtained because of aortic incompetence. In hearts suspended in the upright position, normal coronary anatomy and previously placed coronary occlusions were easily detected in every heart that was read blindly by angiographers. To assess the effects of the contrast media on ventricular performance, five rabbit hearts were harvested and mounted on a Langendorff apparatus for functional analysis at controlled left ventricle volumes. Diastolic and systolic left ventricular pressures were unaffected by the dye injection. This simple and rapid method to evaluate coronary anatomy of the donor heart could be potentially useful in the assessment of older donor hearts in the operating room, thus increasing the volume of donor hearts available for transplantation.

Controlled reperfusion of the regionally ischemic myocardium with leukocyte-depleted blood reduces stunning, the no-reflow phenomenon, and infarct size.

Open-chest sheep underwent 90 minutes' occlusion of the diagonal branch of the left anterior descending coronary artery, followed by vented cardiopulmonary bypass. After 30 minutes of cardioplegic arrest, simulating distal anastomoses, the occlusion on the coronary artery branch was released. Controlled reperfusion (40 to 50 mm Hg, 135 to 150 ml/min) for the first 20 minutes was delivered at the aortic root with either unmodified whole blood (control, n = 7) or blood passed through leukocyte filters (filters, n = 7). Serial measurements were made during 3 additional hours reperfusion off cardiopulmonary bypass. During ischemia, the major determinants of infarct size, which include area at risk, collateral myocardial blood flow, and rate-pressure product were not significantly different between groups. Overall, during reperfusion, mean left ventricular stroke work index in the filter group was greater than in the control group (28.7 +/- 5.8 versus 12.6 +/- 6.4 x 10(3) erg/gm, p less than 0.05), as was mean rate of rise of left ventricular pressure (1900 +/- 260 versus 1348 +/- 279 mm Hg/sec, p less than 0.05). Myocardial blood flow to the area at risk at 3 1/2 hours of reperfusion in the filter group was also significantly better than in the control group (0.57 +/- 0.15 versus 0.27 +/- 0.05 ml/min/gm, p less than 0.05), as was necrotic area as a percentage of area at risk (40% +/- 6% versus 70% +/- 5%, p less than 0.05). These results demonstrate amelioration of myocardial stunning and the no-reflow phenomenon, as well as decreased infarct size. We conclude that controlled reperfusion with leukocyte-depleted blood is superior to whole-blood reperfusion for the surgical treatment of acute regional ischemia.

Ischemic injury before heart transplantation does not cause coronary arteriopathy in experimental isografts.

In this study we investigated whether the duration of ischemia before heart transplantation was related to coronary arteriopathy. Heterotopic cardiac isografts were done in 24 Lewis rats. Group 1 hearts (n = 4) were transplanted immediately after harvesting. Hearts in groups 2 (n = 8), 3 (n = 6), and 4 (n = 6) were implanted after preservation at 4 degrees C for 1, 2, or 3 hours, respectively. No immunosuppressive drugs were given. After 120 days, grafts were removed and evaluated by means of light microscopy for coronary artery intimal proliferation. Minimal intimal thickening was noted throughout, and no differences among the groups were found. Pretransplant ischemia in the absence of other factors does not cause coronary arteriopathy after heart transplantation.

Pulmonary model to predict the effects of series ventricular interaction.

To fully describe the mechanisms of diastolic interaction between the right ventricle and left ventricle, it is necessary to understand how a change in right ventricular output (Qrvo) is transmitted across the pulmonary circulation. This series ventricular interaction is manifest as the temporal response in left ventricular filling (Qlvf) to a change in Qrvo. To quantify series interaction we used a three-element, two-parameter model of the pulmonary circulation. The parameters represented the pulmonary arterial and venous resistance and pulmonary vascular compliance. Using beat-to-beat values of mean pressure and flow measured at the input and output of the pulmonary circulation during the transient response to caval or pulmonary artery occlusion, we estimated the parameters for this model in eight open-chest dogs under control conditions, after autonomic blockade, and after fully opening the pericardium. From 110 separate data episodes, the average values of the pulmonary arterial and venous resistance and pulmonary vascular compliance were 0.14 +/- 0.08 mm Hg.sec/ml and 4.81 +/- 3.17 ml/mm Hg (+/- SD). These estimates were insensitive to the simultaneous effects of autonomic reflexes and direct ventricular interaction, so they uniquely measure the bulk transport properties of the pulmonary circulation. The time constant, which measures the response of Qlvf to a change in Qrvo, averaged 0.26 +/- 0.15 second, which implies that effects of series interaction on Qlvf are manifest within one beat. The model was also able to predict the dynamic response of Qlvf to changes in Qrvo and thus can be used to measure and predict the effects of series interaction in the intact cardiopulmonary system.

Two dimensions describe left ventricular volume change during hemodynamic transients.

Left ventricular (LV) volume can be estimated from three orthogonal dimensions measured by sonomicrometry. Often, an index based on fewer than three dimensions has been substituted for volume. We consider whether a consistent relationship between LV cross-sectional area, computed as the product of the minor axes dimensions and LV three-dimensional volume, is maintained throughout the responses to application and release of vena caval, pulmonary artery, and aortic occlusions, which were held for approximately 30 beats. In six dogs, the relationship between area and volume was highly linear, with an average correlation of 0.98 and standard error of the estimate of 0.9 ml. Within each dog, there were small but statistically significant differences in the intercepts in the regression lines among the three interventions. However, the magnitude of these differences averaged only 0.5 ml. There was not a systematic difference between the relationship for vena caval and pulmonary artery occlusions, and the relationship for aortic occlusions shifted upward by an average of only 0.8 ml. We conclude that cross-sectional area can be substituted for the three-dimensional volume during the transient responses to acute alterations in the external load conditions.

Left ventricular volume measurement by conductance catheter in intact dogs. Parallel conductance volume depends on left ventricular size.

The conductance catheter is a promising new instrument for continuously measuring left ventricular (LV) volume. Absolute LV volume (V[t]) is related to uncorrected conductance volume, B(t), according to the equation: V(t) = (1/alpha)(B(t) - alpha Vc). The alpha Vc factor represents parallel-conductance volume due to conducting material outside the LV blood pool, and may be estimated by transiently changing blood conductivity using a bolus injection of hypertonic saline. alpha is the slope in the relation between B(t) and true LV volume. We tested the assumption that alpha Vc and alpha are constant over a range of hemodynamic conditions. We performed multiple hypertonic saline alpha Vc determinations in seven intact dogs during control conditions and subsequent temporary balloon occlusions of inferior vena cava (IVCO), aorta (AO), and pulmonary artery (PAO). We also compared B(t) with simultaneous biplane angiographic LV volume during similar control and intervention conditions. The saline-derived alpha Vc was 76 +/- 2 ml during control and fell significantly by -7 +/- 2 ml during IVCO (p less than 0.001) but not during AO or PAO. According to multiple linear regression analyses, the strongest predictor of saline-derived alpha Vc was uncorrected end-systolic Bes, with a sensitivity coefficient of 0.60 +/- 0.06 ml/ml (p less than 0.001). Angiographically derived alpha Vc showed a similar dependence on Bes, with a coefficient of 0.77 +/- 0.14 ml/ml (p less than 0.001). Angiographically determined alpha also showed significant variation with hemodynamic interventions, largely reflecting an underlying dependence on alpha Vc. The variation in alpha Vc and alpha with LV size may stem from nonlinearity in the B(t)-V(t) relation. Although the conductance catheter provides a useful measure of relative LV volume, measurement of absolute LV volume over a wide hemodynamic range using constant alpha Vc and alpha factors is unrealistic. This result calls into question the current use of this technique for the measurement of the absolute end-systolic--pressure-volume relation.

Area of the aortic pressure-flow loop measures energy storage by the proximal arteries.

We show that power measured by the area of the pressure-flow loop (APQ) is directly proportional to reactive power [Im(W)], which measures pulsatile energy storage in the proximal arteries. Analytically, Im(W) differs from APQ by K.2 pi, where K is a postulated constant of proportionality. To determine the value of K, 338 heartbeats obtained from 8 dogs under a wide range of hemodynamic conditions were analyzed. The relationship between APQ and Im(W) remained highly linear (r = 0.98), and the pooled value of K was -1.19 +/- 0.01. For the individual dogs, values of K differed at most by +/- 9% from its average value. There was also a small offset in the relationship between APQ and Im(W), probably caused by truncating the calculation of Im(W) at the 10th harmonic. Ignoring the small differences in the values of K and the offset, we found that APQ still proved to be an excellent predictor of Im(W). We also found that APQ was sensitive to changes in heart rate, left ventricular stroke output, and peripheral resistance. This reflects the dependence of pulsatile energy storage on these variables and indicates that APQ cannot serve as an index for changes in just the reactive properties of the proximal arteries.

Haemodynamic consequences of arterial replacement with a synthetic graft.

Because of structural differences between a synthetic graft and the natural artery, a graft would be expected to alter the haemodynamics of the vessel which is bypassed. To examine this, a segment of the lower descending thoracic aorta in six calves was removed and replaced with a Dacron graft. The gradients in pressure and flow across this segment were calculated from simultaneous measurements of pressure and flow made at both ends. From these, the longitudinal (Zl) and transverse (Zt) impedance of the segment was computed. In three animals pressure and flow were measured in the ascending aorta so that the systemic input impedance (Zi) could also be computed. Neither the magnitude nor phase of Zl was affected by the graft. However, the magnitude of Zt was approximately five times higher at all frequencies above DC following insertion of the graft. The characteristic impedance (Zo) was computed from Zl and Zt. Zo for the aortic segment remained approximately constant between 20 and 40 Pa X s X cm-3 for the first 10 harmonics. In contrast, Zo for the graft was strongly frequency dependent, and progressively increased in magnitude up through the tenth harmonic. The input impedance at the entrance to the segment (Zx) was strongly influenced by Zo. As a result, the higher frequency components of Zx were increased following insertion of the graft. In spite of these local changes in impedance, Zi was not affected by the graft. This was probably due to effective filtering by the healthy, compliant aorta left intact between the graft and the left ventricle.