Evaluation of the severity of chronic heart failure by the reactivity of peripheral vessels.

We developed a method to evaluate the severity of chronic cardiac failure by Doppler image analysis. Doppler images of the whole arterial lumen were consecutively recorded on video tape and the power spectrum (sum of intensity multiplied by frequency) of each frame was considered as an index of the blood flow volume (VI). The right brachial artery was occluded for 15-60 seconds by a occluding cuff, and was released quickly. The VI was determined until the VI returned to the level at rest and total VI was calculated as an O2 repayment. The O2 repayment rate (R-Rate) was calculated as a ratio of the O2 repayment divided by total VI during interruption. The cardiac function was evaluated by sub-maximal exercise using bicycle ergometer and was compared with the R-Rate. The subjects were 22 patients (18 males and 4 females) with chronic cardiac failure of NYHA class I (9), class II (6), class III (4), class IV (3) and 12 healthy controls. R-Rate was almost unchanged by the duration of occlusion and showed positive correlation with exercise capacity. R-Rate decreased as the class of NYHA advanced. In conclusion, determination of reactive hyperemia can be used for objectively evaluating the severity of cardiac failure. Doppler sonography; cardiac failure; reactive hyperemia; peripheral circulation

Efficacy of anti-anginal drugs in the treatment of angina pectoris associated with silent myocardial ischemia: importance of quantitative Holter ECG data for patient activity.

METHODS: We evaluated the clinical efficacy of transdermal nitroglycerin (NTG-TTS), a patch application of a nitrate, in the treatment of 27 patients with angina pectoris who had asymptomatic myocardial ischemic (SMI) attacks, using a double-blind cross-over method. Evaluation was made using Holter ECG and patient activity data. RESULTS: In frequency and duration of continuation of SMI episodes, no significant differences were noted between the observation and placebo treatment periods, while the values of both these parameters were decreased significantly in the active drug treatment period compared with those in the observation and placebo treatment periods. Critical heart rate, the heart rate at the initiation of ST-segment depression, was significantly higher during the period of active drug treatment than during the placebo treatment and observation periods. In SMI frequency index, which was determined by adjusting the SMI frequency for the number of steps taken, there were no significant differences between the 3 periods. The SMI time index was significantly lower in the active drug treatment period than in the observation period. CONCLUSIONS: These results indicated that the clinical evaluation of the efficacy of anti-anginal drugs against SMI should take into consideration individual patient activity data.

On an ambulance stretcher suspension concerned with the reduction of patient's blood pressure variation.

The design process and control of an ambulance stretcher suspension to reduce patient's blood pressure variation (BPV) is discussed. The BPV caused by applying the vehicle brakes may lead to deterioration of a patient's condition. The proposed method can reduce BPV by tilting the stretcher and counterbalancing back-to-front acceleration of the ambulance with gravity. The experimental results obtained when using a manually controlled stretcher confirm that BPV is reduced by tilting the stretcher. A continuous control method that varies the tilting angle is investigated through simulation analysis. The results show that this control method reduces the BPV effectively and achieves safe transport of the patient.

Diagnosis of silent myocardial ischemia using ambulatory electrocardiographic monitoring with pedometer, analysis of heart rate, and ST loop in ambulatory electrocardiogram.

BACKGROUND: It has been suggested that episodes of silent myocardial ischemia (SMI) might influence the prognosis of patients with ischemic heart disease, as its consequences are similar to those of myocardial ischemia accompanied by pain. Ambulatory electrocardiogram (ECG) is generally employed in diagnosis as well as in evaluation of clinical efficacy in patients with SMI, but problems related to its application remain because of the difficulty in differentiating between nonischemic and ischemic ST-segment depressions and because of the absence of data concerning body movement. METHODS AND RESULTS: We developed a method for simultaneously recording onto magnetic tape both the ECG chart and pedometer count, as well as a program which enables semi-automatic analysis of the heart rate (HR)-ST relationship. This new method was employed to record ambulatory ECG along with pedometer count for a total of 70 patients, consisting of 53 with coronary heart disease who were shown to have ischemic heart disease, and 17 with various heart diseases in whom coronary angiography revealed no coronary stenosis. The HR-ST relationship was assessed for periods during which steps were recorded by the pedometer, that is, when patients were confirmed to have been under exertion effort. Patients demonstrating the following findings were diagnosed as true positive for SMI: the ST segment level did not decline until HR increased to a certain threshold, and the rate of change in the ST-segment level noted thereafter was -0.025 mm/beats/min or lower; or the ST-segment depression induced by effort continued even after discontinuation of exercise, after which time HR began to decrease, and the HR-ST loop consequently described a counterclockwise rotation. Evaluation of the HR-ST relationship based on these criteria revealed excellent results, as demonstrated by values of 79.2% for sensitivity and 94% for specificity. CONCLUSION: Our newly developed method of assessment of the HR-ST relationship via analysis of simultaneous data from an ambulatory ECG and a pedometer appears to be time saving, highly objective, and useful with regard to the diagnosis of SMI and evaluation of the therapeutic effect of drugs in patients with ischemic heart disease.

Effects of transdermal therapeutic system-nitroglycerin in patients with heart failure. Influence on hemodynamic changes.

Fourteen patients suffering from severe heart failure with 18 mmHg or higher diastolic pulmonary arterial pressure were given a transdermal therapeutic system of nitroglycerin (TTS-NTG). They were evaluated for changes in the hemodynamic responses over 24 hours. Diastolic pulmonary arterial pressure decreased from 27.1 +/- 2.3 mmHg (mean +/- SE) to 22.4 +/- 1.7 mmHg after 1 hour (p less than 0.01), which was maintained throughout the trial. Cardiac index increased from 2.42 +/- 0.13 l/min/m2 to 2.64 +/- 0.16 l/min/m2 after 1 hour (p less than 0.01). The analysis of cardiac and vascular function curves in individual patients suggested that the improvement of hemodynamics was induced mainly in six patients with an increase of contractility and in four patients with a reduction of afterload. No changes were observed in three patients in either contractility or afterload, and a decrease in contractility was seen in one patient. These results suggest that TTS-NTG can be transcutaneously absorbed well enough to produce improved hemodynamic responses in patients with severe heart failure by several mechanisms and maintain these effects over 24 hours.

Effects of changes in afterload impedance on left ventricular ejection in isolated canine hearts: dissociation of end ejection from end systole.

To examine how end systole differs from end ejection and also whether the slope of the end systolic pressure-volume relation can be approximated to that of the end ejection pressure-volume relation, nine isolated, perfused, paced canine hearts ejecting into a hydraulic loading system that simulated the aortic input impedance of a dog's arterial tree were studied. To measure left ventricular volume changes the heart was placed in a plethysmograph. Peripheral resistance (Rp) and arterial compliance (C) were independently varied from 1.9 (Rp = 1.9) to 3.3, 6.4, and 9.6 X 10(8) Pa.m-3.s (Rp run) with a constant value of compliance 1.3 X 10(-9) Pa-1.m3 (C = 1.3), and from C = 0.4 to C = 0.8, C = 1.3 and C = 2.3 (C run) with a constant value of resistance (Rp = 6.4). Five pressure-volume loops were obtained by changing the end diastolic volume at each value of compliance and peripheral resistance. It was clearly shown that ventricular ejection continued after end systole and the time duration between end systole and end ejection became longer with increasing arterial compliance (24(4) at C = 0.4 vs 49(4) ms at C = 2.3, p less than 0.001), while the time duration between end diastole and end systole was constant regardless of afterload impedance change. Regarding the left ventricular pressure-volume relation the end systolic relation was almost linear (r greater than or equal to 0.98) and the slope was not significantly affected by change in any afterload impedance tested. End ejection pressure-volume relation was also linear (r greater than or equal to 0.97) and the slopes in the peripheral resistance and compliance runs were lower than those of the end systolic pressure-volume relation in each corresponding run. The former slopes decreased at smaller values of Rp or larger values of C--namely, 4.4(0.6) at Rp = 9.6 vs 3.6(0.6) at Rp = 1.9, p less than 0.05; 4.8(0.6) at C = 0.4 vs 3.1(0.5) mmHg.ml-1 at C = 2.3, p less than 0.001. Thus it is concluded that end ejection is usually different from end systole and the time difference between them is affected by changes in arterial compliance. In addition, the slope of end ejection pressure-volume relation was dependent on the changes in afterload impedance and cannot be approximated to that of the end systolic pressure-volume relation.

Effects of preload alteration on the degree of ischemia and function of ischemic myocardium under constant mean aortic pressure, coronary perfusion pressure and heart rate in isolated perfused canine heart.

We examined the effects of preload alteration on global and regional (i.e., non-ischemic and ischemic areas) function in the presence of regional myocardial ischemia and on the degree of ischemia using 18 isolated, metabolically supported canine left ventricles. For this purpose, cardiac output (CO), systolic segment length change (SL), myocardial CO2 tension (PmCO2) and ST level of epicardial ECG were measured at 3 levels of left ventricular end-diastolic pressure (LVEDP), i.e., approximately 7 (low LVEDP), 11 (middle LVEDP), and 16 mmHg (high LVEDP) without and with left circumflex artery (LCx) stenosis under a constant mean aortic pressure (90 mmHg), mean coronary perfusion pressure (90 mmHg) and heart rate. In the Pre-ischemic stage, CO and SL increased significantly when LVEDP was elevated in a stepwise fashion by changing the height of the reservoir connected to the left atrium. There were no significant changes in PmCO2 or ST level. On the other hand, with LCx stenosis, CO did not show a subsequent increase at higher LVEDPs (i.e., from 796 +/- 103 ml/min at middle LVEDP to 931 +/- 153 ml/min at high LVEDP). Furthermore, there was no significant SL response in the LCx area following alterations of LVEDP, although there was considerable lengthening of end-diastolic length. Both increased PmCO2 and ST level of the LCx area, following LCx stenosis, further increased significantly with elevation of LVEDP. These results suggest the possibility that considerable elevation of LVEDP worsens the degree of ischemia and does not significantly augment ischemic regional myocardial function or global function, while mild elevation of preload improves or tends to improve simultaneously regional ischemic and global functions without aggravating the ischemic injury significantly. Therefore, we conclude that the preload level is quite important in managing ischemia induced myocardial dysfunction.

A comparison of ST segment deviation and calculated solid angle during acute regional ischemia in the isolated canine heart at precordial, epicardial and intramyocardial lead surfaces.

Although solid angle analysis has been considered to be reasonable for explaining the distribution of ST segment deviation following ischemia, it has not been tested fully, especially for ST segment changes in various sites at different lead surfaces. Thus, we investigated the applicability of solid angle theory to the mechanism of ischemic ST segment deviation at intramyocardial, epicardial and precordial leads. We used seven isolated, coronary perfused, isovolumic contracting canine hearts in a homogeneous cylindrical volume conductor. ST segment potentials from 246 electrodes were continuously measured during left circumflex coronary artery occlusion for five minutes. The ischemic boundary was obtained from a postmortem angiography, and the solid angle subtended by the ischemic boundary was calculated at every electrode site. Despite the difference between epicardial and precordial ST segment potential distributions, there was a high correlation between measured ST segment potential and calculated solid angle at epicardial (r = 0.86 +/- 0.05, 0.77-0.93), precordial (r = 0.93 +/- 0.05, 0.84-0.99), and intramyocardial leads (r = 0.95 +/- 0.03, 0.91-0.99). We conclude that solid angle analysis can be used to approximate the distribution of ischemic ST segment deviation at different lead surfaces in acute ischemia.

Effects of major coronary artery stenosis on the pressure-flow relationship of an adjacent intact coronary artery branch in isolated supported canine left ventricle.

We investigated whether the relationship between the mean left anterior descending and septal coronary blood flow and the mean perfusion pressure varies with left circumflex coronary stenosis. We used excised, perfused canine heart preparations (n = 10), in which variables to influence the myocardial oxygen demand and supply relation can be fairly well controlled. The results showed that coronary blood flow in the adjacent, non-stenosed coronary artery increased significantly following LCX stenosis; this increased flow was found at the same values of heart rate, left ventricular end-diastolic pressure and perfusion pressure, as those in the preischemic state. Moreover, this increased flow was also observed when the values of peak left ventricular pressure and pressure-length loop area were similar between the pre-ischemic and ischemic states. Thus, contributions of neurohumoral factors or alterations in mechanical factors determining the myocardial oxygen demand and supply relation are negligible. This increased flow may be important in maintaining overall cardiac function in cases of acute coronary stenosis or coronary occlusion.

The changes in ECG ST segment and mechanical function of regional ischemic myocardium during afterload reduction in isolated dog hearts with coronary stenosis.

By measuring ECG ST segment deviation and regional mechanical dysfunction, we assessed the effects of an alteration in afterload pressure on regional myocardial ischemia due to a partial coronary occlusion of the left circumflex coronary artery (CFX). Eight isolated, perfused and paced dog hearts were loaded with an artificial arterial system which simulated the aortic input impedance of the dog arterial tree. Afterload pressure was altered by stepwise changes in peripheral resistance (Rp), while left ventricular end-diastolic pressure (LVEDP) and heart rate were kept constant. Coronary perfusion pressure (CPP) was kept equal to mean aortic pressure (AoP). ECG and myocardial systolic segment shortening (SS) were measured in both areas perfused by the CFX and the left anterior descending coronary artery (LAD). In the presence of CFX stenosis, mean AoP decreased from 96 +/- 7 to 46 +/- 7 mmHg following a decrease in Rp and cardiac output increased progressively from 465 +/- 30 to 1055 +/- 100 ml/min. In this situation, CFX coronary blood flow decreased from 75 +/- 2 to 28 +/- 6 ml/100 g/min. Epicardial ECG in the ischemic region showed two types of ST segment deviation after CFX stenosis: ST segment elevation and ST segment depression. Moreover, following afterload reduction, these individual ECG ST segment changes showed further deviations. The levels of mean AoP, below which further ST segment deviations significantly occurred, were as follows: 71 +/- 6 mmHg in ST segment elevation cases and 52 +/- 7 mmHg in ST segment depression cases. Myocardial systolic segment shortening in the ischemic region also significantly decreased following CFX stenosis (91 +/- 8% of pre-ischemic control, p less than 0.05). Then, during afterload reduction, SS in the CFX area appeared to be bimodal and it definitely decreased when mean AoP was 46 +/- 7 mmHg. To enhance the sensitivity of detection of further mechanical dysfunction throughout afterload reduction following regional myocardial ischemia, we calculated percentage values of the SS in the CFX area to the SS in the LAD area at each Rp. By this normalization, mechanical dysfunction was found when mean AoP was below 67 +/- 5 mmHg. These results suggest that reduction in afterload pressure below a certain level aggravated the regional ischemia, despite an increase in cardiac output, and to detect this change in the ischemic region during afterload reduction, ECG ST segment deviation seems to be a useful indicator.(ABSTRACT TRUNCATED AT 400 WORDS)

The influence of changes in the size of ischemic region on ST-segment potential distribution in isolated canine hearts.

In order to investigate how a change in the size of a ischemic region is reflected in ST-segment mapping studies, we produced two different sizes of ischemic regions by occluding proximal or distal portions of the left circumflex artery for five minutes, using ten isolated canine heart preparations. We examined the relationship between the geometry of the ischemic region and ST-segment potential distribution on the epicardial surface and that in the "precordium", in which the heart was suspended. The extent of the ischemic region was reflected differently on epicardial and "precordial" sites, in that the magnitude of epicardial ST-segment elevation decreased (p less than 0.001) while the "precordial" one increased (p less than 0.01). In the epicardium the degree of ST-segment elevation was almost uniform over the ischemic region, whereas in the "precordium" it was maximal at sites overlying the center of the ischemic region and progressively decreased approaching the periphery. However, frequent occurrence of intraventricular conduction disturbance was observed near the center of the ischemic region. As a result, the magnitude of epicardial ST-segment elevation near the center became larger than in the periphery. These results suggest that the classical solid angle theory provides a useful approximation of the ST-segment deflection in very acute ischemic phase, until development of the intraventricular conduction delay.

Effects of OPC-8212, a new positive inotropic agent, and dobutamine on left ventricular global and ischemic regional functions and coronary hemodynamics under coronary artery stenosis.

We have investigated the effects of OPC-8212, a new positive inotropic agent, and dobutamine, a known cardioselective inotropic agent, on global left ventricular (LV) and ischemic regional functions in 14 excised canine hearts with a flow-limiting stenosis of the left circumflex coronary artery (LCX) (i.e., 20-25% of control flow). OPC-8212 infusion (n = 7) under LCX stenosis improved cardiac depression [i.e., peak LV dP/dt increased from 1,295 +/- 143 mm Hg/s to 2,669 +/- 266 mm Hg/s (mean +/- SEM) (p less than 0.001)], while myocardial ischemic injury, assessed by myocardial CO2-tension and electrocardiogram (ECG)-ST changes, improved (i.e., delta CO2-tension and ECG-ST deviation decreased from 21.1 +/- 3.6 mm Hg and 3.8 +/- 0.6 mV to 13.3 +/- 2.8 mm Hg (p less than 0.01) and 2.0 +/- 0.7 mV (p less than 0.05), respectively). On the other hand, dobutamine infusion (n = 7) further increased myocardial CO2-tension and ECG-ST deviation [i.e., delta CO2-tension and ECG-ST deviation increased from 14.4 +/- 4.2 mm Hg and 2.5 +/- 1.2 mV to 29.0 +/- 6.0 mm Hg (p less than 0.01) and 4.9 +/- 1.0 mV (p less than 0.01), respectively]. At the same time, peak LV dP/dt clearly improved, but to a lesser degree; from 1,425 +/- 153 mm Hg/s to 2,393 +/- 245 mm Hg/s (p less than 0.001). There was also an increase in percent systolic segment shortening of each corresponding area as with OPC-8212.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of coronary artery stenosis on left ventricular end-ejection pressure-ejected volume relationships in isolated perfused canine hearts.

We investigated the behavior of the left ventricular end-ejection pressure-ejected volume relation with and without left circumflex coronary stenosis in isolated perfused canine hearts. To change ventricular afterload pressure, the peripheral resistance of the hydraulic model attached to the aortic root of the excised hearts was changed in a stepwise fashion to five different levels. The end-ejection pressure-ejected volume relationship was nearly linear in both pre-ischemic and ischemic states. The slope changes following left circumflex coronary stenosis differed among the hearts used in the present study, and there was no significant difference in average slope (n = 10) between the pre-ischemic and ischemic states (i.e., -7.4 +/- 1.0 and -8.4 +/- 1.2 mmHg/ml, respectively). Therefore, the, slope of the relation was not useful in judging the presence of depressed ventricular function induced by coronary stenosis. In contrast, the ejected volume axis intercept decreased significantly from 16.5 +/- 1.1 ml to 13.6 +/- 1.1 ml (p less than 0.05) with regional ischemia.

ST segment changes under occlusion of the proximal portion of major coronary arteries in the isolated canine heart.

We studied the mechanisms of ST segment displacement in the ECG recorded from the epi- and subendocardium of ischemic ventricles in the isolated and perfused canine heart. ST segment changes were observed in association with a relatively large area of ischemia produced by occlusion of the left anterior descending and septal arteries (LAD + Sept.) or of the left circumflex artery (LCx). Contrary to previous reports, we found that the amount of subendocardial ST elevation was not always greater than that in the epicardial ECG recorded at the center of ischemia. Also, in the non-ischemic area, the degree of the ST depression in the subendocardial record was nearly the same as the epicardial record. On the other hand, the degree of the epicardial ST elevation on the border zone was always smaller than that at the ischemic center, which seemed to be due to the broadness of the border zone. The amplitude of the ST depression in the non-ischemic area was greater when the recording electrode was near the ischemic border, which supports the solid angle theory. The degrees of both ischemic ST elevation and reciprocal ST depression in the LCx perfused area were always greater than in the LAD + Sept. perfused area. These results strongly suggest that ST segment displacement depends on the relative position of the recording electrode to the electric double layer which exists at the border between the ischemic and non-ischemic area.

A new indirect method for measurement of sinoatrial conduction time and sinus node return cycle.

We developed a new indirect method for the measurement of sinoatrial conduction time (SACT) and the sinus node return cycle (SRC) with a transvenous catheter technique. Two early premature stimuli, at intervals 50 msec longer than the effective refractory period (ERP), were given to the right atrium. These early stimuli were followed by eight constant stimuli. The interval of the constant stimuli was a little shorter than the basic cycle length (BCL). The return cycle A1Ar was measured and plotted on the abscissa; the next interval ArA3, was measured and plotted on the ordinate. This was called the "base point". A new stimulus, A2, was then added to the train of stimulations, first at a point simultaneous with Ar. It was then shifted toward the last constant stimulus at 10-20 msec intervals until A2 met the ERP. The relationship between A1A2 and A2A3 was obtained by the repetition of the procedures with various A1A2 intervals. It had two zones, compensatory and non-compensatory. We postulate that the atriosinus conduction time of the last of the eight stimuli was equal to that of A2 when the stimulus A2 first captured and reset the sinus nodal pacemaker cells, as indicated by the transition point of the two zones. Based on this supposition, SACT and SRC could be measured as the intervals from the base point to the transition point and from the transition point to the eighth stimulus, respectively.

The effect of heart rate and left ventricular end-diastolic pressure on the direction of ST segment displacement in acute ischemia.

The correlation between the ST segment displacement and coronary blood flow in various hemodynamic conditions was studied. Five isolated, isovolumic contracting canine hearts were used. The left main and the right and left circumflex (LCx) coronary arteries were cannulated and perfused with support dog's arterial blood. Four pairs of Ag-AgCl ECG electrodes were attached to the epicardium and subendocardium in the LCx perfused area. Heart rate and left ventricular end-diastolic pressure (LVEDP) were controlled by means of right atrial electrical pacing and infusion or withdrawal of arterial blood into the left ventricle, respectively. LCx flow was reduced by 75, 50, 25% of the control level under the condition of 200 beats/min of heart rate and 20 mmHg or 5 mmHg of LVEDP, and ECGs were recorded. The ST segment elevation was observed in epi- and subendocardial lead ECGs when LCx flow was reduced from 110 +/- 27.5 ml/min/100 g to 72 +/- 3 ml/min/100 g under the condition of normal LVEDP (5 mmHg) and a high heart rate (200 beats/min), whereas the same degree of reduction in LCx flow under the condition of high LVEDP (20 mmHg) and high heart rate (200 beats/min) resulted in an epicardial ST segment depression associated with marked subendocardial ST segment elevation. The results suggest that the coronary flow reduction with a higher LVEDP will induce subendocardial ischemia, whereas the same degree flow reduction with a normal LVEDP induce transmural ischemia.

The relationship between myocardial oxygen consumption and total work obtained by a new left ventricular model.

The relationship between myocardial oxygen consumption (MVO2) and left ventricular work was examined experimentally, assuming that the left ventricle is equivalent to an electrical current source generator consisting of parallel source resistance (Ri) and constant generator current (I0). The internal and external work can be calculated as (Ri X I1(2)) and (Rp X I2(2)) in this model, where I1 is current of source resistance, Rp is peripheral resistance and I2 is cardiac output. The experiments were performed with a blood-perfused isolated ejecting canine heart preparation in which the hydraulic model, simulated to an aortic input impedance, was attached to the aortic root. The peripheral resistance was changed in a stepwise fashion and left ventricular pressure, cardiac output and MVO2 were measured. The calculated total work showed a close linear correlation with the MVO2, which suggested that the left ventricle can be regarded as a current source generator and the total work as a main mechanical factor in determining the MVO2.

Experimental study on vasodilator therapy and its clinical application.

To evaluate the effects of vasodilator therapy, the quantitative relationships between peripheral resistance, LVEDP, coronary circulation and cardiac output were analyzed by using 23 isolated coronary perfused canine heart which afterload, preload, 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 ( physiologically 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.

Pressure-length loop in the ischemic segment during left circumflex coronary artery stenosis and its modification by afterload reducing in excised perfused canine hearts.

By using excised perfused heart preparations, we investigated the regional myocardial functions in the presence of a flow-limiting coronary stenosis of the left circumflex coronary artery (LCX) (approximately low reduction of pre-ischemic control), as well as global cardiac functions during afterload reducing, while keeping left ventricular end-diastolic pressure (LVEDP) and heart rate constant. After inducing the LCX stenosis, cardiac output (CO), peak left ventricular pressure (peak LVP) and stroke work (SW) decreased from pre-ischemic control values, i.e., 81.1 +/- 3.2%, p less than 0.005, 88.1 +/- 3.8%, p less than 0.02 and 72.2 +/- 5.7%, p less than 0.005, respectively (n = 7), whereas pressure-length (P-L) loop areas changed as follows; ischemic control values of the left anterior descending coronary artery (LAD) and LCX regions were 96.6 +/- 6.0%, n.s. and 72.6 +/- 9.0% of pre-ischemic control, p less than 0.02, respectively. Following afterload reducing with LCX stenosis, CO increased gradually, while the ischemic regional function started to further aggravate, and the initial point of further ischemic aggravation obtained in this experiment occurred at 63.5 +/- 6.9 mm Hg of mean aortic pressure (AoP). These results suggested that the increase of total cardiac function such as CO following afterload reducing was probably induced at the expense of aggravated regional ischemia. Therefore it was concluded that the treatment of ischemic myocardium by reducing afterload pressure should be done very carefully.