The feasibility of the thermodilution technique to measure cardiac output (CO) during positive pressure ventilation was assessed in 12 critically ill patients. An indicator (5 ml of 5% glucose in cold water) was injected at the mid and end of the inspiratory and expiratory phases of mechanical ventilation to see the effects of the respiratory cycle on thermodilution data. The 36 measurements at mid-inspiration yielded the smallest coefficient of variation (CV), 2.7%. The CV of 36 randomly selected measurements was 6.0%. CO at end-inspiration gave the highest value (p<0.05). These data suggested that one major disadvantage of the thermodilution method, the need for repeated measurement to minimize the variation in data, could be overcome by timing the injection according a certain phase of mechanical ventilation.

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Decreased cardiac performance during ventricular tachycardia or ventricular pacing has been ascribed to the lack of synchrony due to altered ventricular contraction. However, the direct effect of the pacemaking site on blood flow in the major coronary arterial branches and on regional contractile forces has not been adequately examined. In this investigation, twelve dogs were used to assess coronary flow in the left anterior descending (LAD) and circumflex coronary arteries (LCx) and the regional myocardial function in response to ectopic electrical pacing. The sites were the outflow tract of the right ventricle (RV pacing), the anterior left ventricular wall suppled by the LAD (LAD pacing), and the lateral wall perfused by the LCx (LCx pacing). Strain gauge arches were transmurally fixed to myocardial segments of the anterior and lateral walls of the left ventricle. The mechanical forces generated were measured while simultaneously recording blood flow in the LAD and LCx. RV pacing diminished developed-tension similarly in both areas. LAD flow was further decreased during anterior pacing as was the developed-tension in the LAD supplied area. A similar relationship was observed between LCx flow and developed-tension in the LCx area during lateral pacing. Compared to RV pacing, anterior pacing did not affect LCx flow and local myocardial force in the lateral wall of the left ventricle, and lateral pacing did not cause further changes in LAD flow and anterior myocardial function. The decrements in blood flow were closely related to decreased myocardial function (p<0.01). These findings indicate that ventricular pacing decreases ventricular performance with attenuated regional myocardial function at the pacing area, in addition to causing altered ventricular contraction sequence.

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Duplication of the tricuspid valve is a rare congenital cardiac anormaly. We experienced one infant case with Ebstein anomaly, who died at seven months of age. At autopsy, the clinical diagnosis was confirmed, and also the patient was found to have double tricuspid valve orifices, each of which were accompanied by subvalvular tension apparatuses. Tricuspid valve leaflets seen in Ebstein anoamly are known to have fenestrations as accessory orifices for some instances, but this case is unique and interesting in that each valve orifice has well-developed chordae tendinae and papillary muscles below it.

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The factors associated with the development of pump failure in patients with acute myocardial infarction (MI) were studied in 475 patients admitted to our coronary care unit (CCU) and a clinical and hemodynamic re-evaluation of vasodilator and catecholamine therapy was carried out in patients with pump failure. The severity of pump failure as represented by Killip's classification was closely related to left ventricular (LV) dysfunction as judged by LV ejection fraction, number of previous MIs and peak creatinine phosphokinase (CPK) value, and the severity of coronary atherosclerotic lesions as assessed by coronary arteriography. Retrospective hemodynamic analysis of vasodilator therapy (intravenous nitroglycerin, nitroprusside and phentolamine) in 94 patients with pump failure revealed that a significant decrease in pulmonary capillary wedge pressure (PCW) with no significant change in cardiac index (CI) resulted in a clinical improvement in pulmonary congestion in Forrester's hemodynamic subset 2. However, in patients in subsets 3 and 4, the slight increase in CI induced by vasodilator therapy was not enough to restore normal systemic perfusion in spite of a significant decrease in PCW and total systemic resistance; catecholamine was far more effective in increasing CI. Thus, the major indication for vasodilator therapy is in patients of subset 2, while combined use with catecholamine is preferable in those with low cardiac output.

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We evaluated long-term combine vasodilator therapy (hydralazine or ecarazine + isosorbide dinitrate) in 29 patients with chronic congestive heart failure resistant tot the optimal conventional therapy. There were 24 men and 5 women, aged 28 to 76 years (mean 52 y/o). The etiology of heart failure was congestive cardiomyopathy in 24 patients, ischemic cardiomyopathy in 4 patients and advanced mitral regurgitation due to calcified mitral annulus in 1 patient. There were 21 patients in NYHA class III and 8 patients in NYHA class IV. All patients continued their previous therapeutic regimen during the period of this study. Hemodynamic measurements were performed with a triple lumen flow-directed baloon-tipped catheter in 20 patients to evaluate the effects of vasodilator therapy. In the rest of 9 patients, heart rate, blood pressure, chest X-ray examination for heart size (CTR) and M-mode echo-cardiograms for ejection fraction (EF) were monitored. The hemodynamic responses to the combined vasodilator therapy in 20 patients showed significant decreases in afterload and preload concomitant with an increase in cardiac output. The noninvasive evaluation of combined vasodilator therapy in 9 patients resulted in significant improvement in CTR and EF. We also noted a significant improvement in their symptoms of 29 patients. Side effects and drug toxicity were uncommon during vasodilator therapy. It is concluded that the combined vasodilator therapy is most useful adjunctive therapy in the management of severe refractory heart failure. Moreover, long-term nonparenteral vasodilators can be administered even at outpatient clinic without hemodynamic monitoring.

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The effects of PGE₁ and ISD on right ventricular performance in patients with pulmonary hypertension secondary to chronic lung disease were evaluated, and the following results were obtained. I) Effects of PGE₁ on Right Ventricular Failure The effects of PGE₁ (intravenous infusion, 0.01 to 0.03 μg/kg/min) on right ventricular failure were studied in 12 patients with acute exacerbation of chronic respiratory failure. PGE₁ resulted in a significant fall in RAP (p<0.05), PAMP (from 33.8±7.6 to 29.3±5.7 mmHg, p<0.005) and TPVR (p<0.001), whereas a significant increase in CI (from 3.4±0.6 to 3.9±0.61/min/m²), p<0.001) and SI (p<0.005). PaO₂ was significantly decreased by PGE₁ (p<0.02), however p_v^^-O₂ remained unchanged because of a significant increase of O₂-transport (p<0.01). PGE₁ induced active vasodilation of the pulmonary vascular beds and reduced a right ventricular afterload. We concluded that PGE₁ improved the right ventricular failure secondary to chronic lung disease. II) Effects of ISD on Right Ventricular Performance The effects of ISD (intravenous infusion, 0.05 mg/kg/hr) on right ventricular performance were studied at rest and during exercise in 11 patients with clinically stable chronic respiratory failure. At rest and during exercise, ISD induced a significant decrease in RAP, PAMP and CI, however no change in TPVR. RVWI was reduced significantly by ISD (from 2.5±0.8 to 1.9±0.5 kg·m/min/m², p<0.01) during exercise. ISD reduced the right ventricular preload by means of venodilation, and reduced right ventricular work. We concluded that ISD improved the right ventricular performance of cor pulmonale.

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Therapy to decrease the load in congestive heart failure is now classified as acute and chronic vasodilator therapy. In this symposium, we presented prostacycline (PG I₂) as an acute and prazosin as a chronic vasodilator. Their hemodynamic and clinical effectiveness were evaluated and their effect on the sympathetic nervous system was also studied. We studied the effect of intravenous prostacyclin infusion in doses of 22±11 ng/kg/min in nine patients with severe congestive heart failure refractory to digitalis and diuretic drugs. After prostacyclin infusion, mean pulmonary capillary wedge pressure decreased from 21.0±7.9 to 15.0±6.6 mmHg (p<0.001), mean arterial pressure from 98.9±12.8 to 76.2±7.0 mmHg (p<0.001), systemic vascular resistance from 2, 574±384 to 1, 368±283 dynes·sec·cm^-5 (p<0.001), pulmonary vascular resistance from 1, 008±451 to 443±135 dynes·sec·cm^-5 (p<0.001) and pulmonary arteriolar resistance from 330±111 to 189±73 dynes·sec·cm^-5 (p<0.001). The cardiac index increased from 2.0±0.37 to 3.2±0.591/min/m² (p<0.001), and the stroke index from 27.6±8.69 to 42.0±0.62 ml/m² (p<0.001). Moreover, prostacyclin therapy counteracted the sensation of coldness of the limbs and face, and patients felt warmth and mild flushing of the face. The effect of prazosin on the exercise duration time until dyspnea was evaluated by the treadmill test. In comparison with a placebo, prazosin significantly increased this time from 11.4±5.6 min to 13.0±5.8 (p<0.005) and significantly reduced systolic blood pressure from 121±22 mmHg to 114±20 (p<0.005). These data suggest that prazosin is effective in treating chronic left ventricular failure. The effect of vasodilators on the sympathetic nervous system in congestive heart failure is not known. After prostacyclin therapy, plasma norepinerphrine levels did not change significantly (824±375 pg/ml vs 880±468, NS). During chronic therapy with prazosin, plasma norepinerphrine levels increased significantly (766±209 pg/ml vs 416±209 with placebo, p<0.001). When mean pulmonary capillary wedge pressure was maintained at around 15 mmHg by oral prazosin administration, prazosin increased the plasma norepinerphrine level significantly. (384±141 to 450±121 [1 hr, p<0.001], 580±161 [2 hr, p<0.001], 504±98 [3 hr, p<0.001]). These results suggest that the sympathetic nervous system may play an important role in congestive heart failure during both acute and chronic vasodilator therapy.

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To evaluate the effects of vasodilator therapy, the quantitative relationships between peripheral resistance, LVEDP, coronary circulation and cardiac output were analyzed by using 23 isolate coronary perfused canine heart which afterload, coronary blood flow and heart rate are able to regulate independently. Peripheral resistance was decreased incrementally to lower mean arterial pressure from 107-97 mmHg to 48-22 mmHg keeping preload and heart rate at constant level. A decrease in mean arterial blood pressure to 72 (physiologicaly coronary perfused heart) and 68 mmHg (coronary stenosed model) increased cardiac output, respectively. However, myocardial oxygen consumption in each group decreased under 5.5 ml/min/100g LV which suggested myocardial ischemia worsen and further decrease in blood pressure lowered cardiac output. LVEDP also decreased incrementally from 18-20 mmHg to 5 mmHg keeping afterload at 100 mmHg of mean arterial blood pressure constantly. A decrease in LVEDP from 20 to 14 mmHg reduced stroke work index in normal heart but increased slightly in failing heart. Further lowering in LVEDP resulted decreasing in stroke work index in both group. Thus modest and adequate reduction in preload and afterload has beneficial effects to cardiac function. In contrast, further decrease will worsen myocardial perfusion and cardiac function.

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Hemodynamic effects of vasodilator agents (molsidomine, nitroglycerin, isosorbide dinitrate or prostaglandin I₂) were studied in 53 patients with acute myocardial infarction. In 20 of these patients, effect on cardiac metabolism were also studied. Patients were divided into four groups according to the Forrester subset and hemodynamic effects of these agents were evaluated by the cardiac index (CI)-preload (PAEDP) relationship. In patients of Forrester subset II and IV, vasodilators were capable of producing a considerable reduction in preload without a significant decrease in cardiac output. However, in patients of Forrester subset IV, five of six patients had only a minimal improvement in cardiac performance with vasodilator therapy because of a severe pump failure. In these patients, a combination therapy with dopamine was necessary to maintain the cardiac output. In patients with Forrester subset III, vasodilator therapy decreased cardiac index and preload was also reduced. Thus, for these patients vasodilators could not be indicated but volume infusion may be indicated. In patients with Forrester subset I, although vasodilator therapy decreased cardiac output, coronary sinus flow and myocardial oxygen consumption were also decreased, indicating that the vasodilator therapy is also beneficial for patients even without heat failure because of the protective effect of unloading on ischemic myocardium. Three nitrate agents, i.e., molsidomine, nitroglycerin and isosorbide dinitrate, demonstrated the similar effect on hemodynamics; mean blood pressure and PAEDP decreased by 7-10% and 20-29%, respectively, while systemic vascular resistance was not significantly decreased. In contrast to nitrates, PGI₂ decreased mean blood pressure and systemic vascular resistance significantly, whereas a decrease in PAEDP was minimal. Although the present study focused on the acute effects of vasodilators on ischemic heart, we demonstrated that the vasodilator therapy is effective for improving the cardiac performance or salvaging the jeopardized ischemic myocardium in patients with acute myocardial infarction except for patients of Forrester subset III.

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There have been yet only a few studies on the action of vasodilators on the entire systemic capacitance vessels of the living body. In the present study, we studied the action of the vasodilators on the systemic capacitance vessels by measuring the mean circulatory pressure (MCP), introduced by Guyton, and that on the systemic resistance vessels from total peripheral resistance, in anesthetized open chest dogs. We also studied the venous return curves. Depending n vasodilators and the dosages used, resistance vessels could be dilated, but capacitance vessels could not be dilated. The reverse was never true. It was also found frequently that capacitance vessels could be dilated only when the tone of the capacitance vessels have been previously elevated by norepinephrine. Again, depending on vasodilators and their dosages, the venous return curves were changed in position and/or slope. We constructed a venous return curve by connecting 2 points on the venous return-right atrial pressure (VR-RAP) plane, one, VR-RAP plot, and the other, the point of VR=0, RAP=MCP. Changes in the venous return curve caused by these vasodilators were classified into three types; (a) a clockwise rotation with a constant MCP, where one sees no change in MCP and decreased resistance to venous return (RVR), so that one may call this RVR-type, (b) a parallel shift of the venous return curve to the left, where one sees no change in RVR but a decreased MCP, so that one may call this MCP-type and (c) a shift to the left plus clockwise rotation, where one sees a decrease in MCP and decrease in RVR, so that this is a mixture of patterns (a) and (b). One may call this the mixed-type. The existence of the response of mixed-type is worth special attention, because, in this type, cardiac output (CO) was increased by the predominant decrease in RVR in spite of a decreased MCP, leading to an important condition that the CO does not necessarily decrease when systemic capacitance vessels were dilated by the vasodilators.

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The effects of nitroprusside (NP) on hemodynamics, especially on venous flow velocity of the inferior vena cava (IVC) were evaluated in 20 remote myocardial infarction patients. NP was given begining at 10 μg/min, with subsequent increments of 10 μg/min every 5 minutes until the systolic blood pressure was reduced to about 30 mmHg. Pressure was measured by a catheter-tip micromanometer. Flow velocity of IVC was measured by a catheter-tip flow velocity probe. NP significantly decreased left ventricular systolic pressure, left ventricular end-diastolic pressure, mean aortic pressure, right ventricular systolic pressure, right ventricular end-diastolic pressure, mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure, systemic vascular resistance index (SVRI) and left ventricular volume. Cardiac index (CI) was unchanged and stroke volume index was decreased. IVC pressure was unchanged, while right atrial (RA) pressure decreased. Subsequently, the pressure difference between IVC and RA increased significantly. The amplitude of IVC flow velocity decreased significantly. Twenty patients were classified into two groups according to whether or not the CI increased by NP. CI increased in 9 patients (group I) and decreased in 11 patients (group D). Compared to group D, control CI and the slope of end-systolic pressure-volume relation were less and the difference between IVC pressure and RA pressure was greater in group I. The patients with higher control SVRI had greater increase in CI during NP. In our study, the greater the depression of cardiac performance and the higher the SVRI, the greater the improvement of left ventricular pumping function during NP.

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For the last 20 years, vasodilator drugs have been used for the therapy of congestive heart failure. During this period, there has been increasing interest in the treatment of congestive heart failure. Vasodilators are divided into one which reduced preload, another which reduces after-load and the last which has both effects. Changes in cardiac output causes changes in distribution of cardiac output to each organ. Therefore, after vasodilators injection, changes in systemic distribution of blood flow should not be equal in each organ. In this report, changes in systemic distribution of cardiac output after vasodilator injection are discussed. Systemic distribution of blood flow in normal circulation differs from that in abnormal circulation. In this report, effects of vasodilators on systemic distribution of cardiac output in the state of experimentally created heart failure are discussed.

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