Altered maternal left ventricular contractility and function during normal pregnancy.

OBJECTIVES: To evaluate maternal left ventricular (LV) systolic and diastolic function during normal pregnancy by non-invasive measures of LV contractility incorporating loading conditions. METHODS: Sixty-five women were examined using echocardiography, including tissue Doppler and two-dimensional speckle tracking, and subclavian artery pulse trace recordings at gestational weeks 14-16, 22-24 and 36, and at 6 months postpartum. RESULTS: The mean ± SD age of the women was 32.0 ± 4.6 years. Cardiac output and LV end-diastolic volume were on average 20% and 23% higher, respectively, during pregnancy, compared to that at 6 months postpartum (both, P < 0.01). LV ejection fraction, global peak systolic strain and rate-corrected LV velocity of circumferential fiber shortening (Vcfc) were 11%, 6% and 6% lower, respectively, at 36 weeks' gestation compared to at 6 months postpartum (all, P < 0.01). Afterload, measured as LV end-systolic wall stress (ESWS) increased by 10% between 14-16 and 36 weeks' gestation (P < 0.01). Analysis of the relationship between Vcfc and ESWS revealed that LV contractility was lower during pregnancy than at 6 months postpartum. Changes in diastolic function were demonstrated by 11% lower mitral early diastolic (E) wave velocity, 8% lower tissue Doppler early diastolic velocity (e') and 13% higher left atrial area (all P < 0.01) during pregnancy. Tissue Doppler E/e' remained unaltered (P = 0.78). CONCLUSIONS: During normal pregnancy, LV contractility is lower than it is at 6 months postpartum. This is associated with increased LV and left atrial area, whereas filling pressures are unchanged. These findings suggest that pregnancy exerts a larger load on the cardiovascular system than previously assumed.

Prognostic utility of the assessment of diastolic function in patients undergoing cardiac resynchronization therapy.

Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. Aims of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. METHODS AND RESULTS: One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI: 0.14-0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06). CONCLUSIONS: The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response.

Deceleration time of systolic pulmonary venous flow: a new clinical marker of left atrial pressure and compliance.

The curvilinearity of the atrial pressure-volume curve implies that atrial compliance decreases progressively with increasing left atrial (LA) pressure (LAP). We predicted that reduced LA compliance leads to more rapid deceleration of systolic pulmonary venous (PV) flow. With this rationale, we investigated whether the deceleration time (t dec) of PV systolic flow velocity reflects mean LAP. In eight patients during coronary surgery, before extracorporeal circulation, PV flow by ultrasonic transit time and invasive LAP were recorded during stepwise volume loading. The t dec was calculated using two methods: by drawing a tangent through peak deceleration and by drawing a line from peak systolic flow through the nadir between the systolic and early diastolic flow waves. LA compliance was calculated as the systolic PV flow integral divided by LAP increment. Volume loading increased mean LAP from 11 +/- 3 to 20 +/- 5 mmHg (P < 0.001) (n = 40), reduced LA compliance from 1.16 +/- 0.42 to 0.72 +/- 0.40 ml/mmHg (P < 0.004) (n = 40), and reduced t dec from 320 +/- 50 to 170 +/- 40 ms (P < 0.0005) (n = 40). Mean LAP correlated well with t dec (r = 0.84, P < 0.0005) (n = 40) and LA compliance (r = 0.79, P < 0.0005) (n = 40). Elevated LAP caused a decrease in LA compliance and therefore more rapid deceleration of systolic PV flow. The t dec has potential to become a semiquantitative marker of LAP and an index of LA passive elastic properties.

Wasted septal work in left ventricular dyssynchrony: a novel principle to predict response to cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) in heart failure is limited by many non-responders. This study explores whether degree of wasted left ventricular (LV) work identifies CRT responders. METHODS AND RESULTS: Twenty-one patients who received CRT according to guidelines were studied before and after 8 ± 3 months. By definition, segments that shorten in systole perform positive work, whereas segments that lengthen do negative work. Work was calculated from non-invasive LV pressure and strain by speckle tracking echocardiography. For each myocardial segment and for the entire LV, wasted work was calculated as negative work in percentage of positive work. LV wall motion score index (WMSI) was assessed by echocardiography. Response to CRT was defined as ≥15% reduction in end-systolic volume (ESV). Responder rate to CRT was 71%. In responders, wasted work for septum was 117 ± 102%, indicating more negative than positive work, and decreased to 14 ± 12% with CRT (P < 0.01). In the LV free wall, wasted work was 19 ± 16% and showed no significant change. Global LV wasted work decreased from 39 ± 21 to 17 ± 7% with CRT (P < 0.01). In non-responders, there were no significant changes. In multiple linear regression analysis, septal wasted work and WMSI were the only significant predictors of ESV reduction (ß = 0.14, P = 0.01; ß = 1.25, P = 0.03). Septal wasted work together with WMSI showed an area under the curve of 0.86 (95% confidence interval 0.71-1.0) for CRT response prediction. CONCLUSION: Wasted work in the septum together with WMSI was a strong predictor of response to CRT. This novel principle should be studied in future larger studies.

Mechanisms of retarded apical filling in acute ischemic left ventricular failure.

BACKGROUND: We examined the hypothesis that retardation of apical filling as measured by color M-mode Doppler echocardiography in the diseased left ventricle (LV) reflects a decrease in the intraventricular mitral-to-apical pressure gradient. METHODS AND RESULTS: In 9 open-chest anesthetized dogs, micromanometers were placed near the mitral tip and in the apical region. From the color M-mode Doppler images, the time delay (TD) between peak velocity at the mitral tip and the apical region was determined as an index of LV flow propagation. Acute ischemic LV failure was induced by coronary microembolization. Induction of ischemia caused a marked increase in LV end-diastolic pressure and a decrease in LV ejection fraction. The time constant of LV isovolumic apical pressure decay (tau) increased from 31+/-8 to 49+/-16 ms (P<0.001). The peak early diastolic mitral-to-apical pressure gradient (DeltaPLVmitral-apex) decreased from 1.9+/-0.9 to 0.7+/-0.5 mm Hg (P<0.01), and TD increased from 5+/-3 to 57+/-26 ms (P<0.001). The slowing of flow propagation was limited to the apical portion of the LV cavity. The TD correlated with DeltaPLVmitral-apex (r=-0.94, P<0.01) and with tau (r=0.92, P<0.01). Before ischemia, the mitral-to-apical flow propagation velocity far exceeded the velocity of the individual blood cells, whereas during ischemia, flow propagation velocity approximated the blood velocity. CONCLUSIONS: Retardation of apical filling in acute ischemic failure was attributed to a decrease in the mitral-to-apical driving pressure, reflecting slowing of LV relaxation. The slowing of flow propagation appeared to represent a shift in apical filling from a pattern of column motion to a pattern dominated by convection.

Myocardial strain by Doppler echocardiography. Validation of a new method to quantify regional myocardial function.

BACKGROUND: Myocardial strain is a measure of regional deformation, and by definition, negative strain means shortening and positive strain, elongation. This study investigates whether myocardial strain can be measured by Doppler echocardiography as the time integral of regional velocity gradients, using sonomicrometry as reference method. METHODS AND RESULTS: In 13 anesthetized dogs, myocardial longitudinal strain was measured on apical images as the time integral of regional Doppler velocity gradients. Ultrasonic segment-length crystals were placed near the left ventricular (LV) apex and near the base. Apical ischemia was induced by occluding the left anterior descending coronary artery (LAD), and preload was increased by saline. Percentage systolic strain by Doppler correlated well with strain by sonomicrometry (y=0.82x-1.79, r=0.92, P<0.01). During LAD occlusion, apical myocardium became dyskinetic, as indicated by positive strain values and negative Doppler velocities. At the LV base, myocardial strain by Doppler, strain by sonomicrometry, and velocity of shortening by sonomicrometry (dL/dt) were unchanged during apical ischemia. However, myocardial Doppler velocities at the base decreased from 4.2+/-0.7 (+/-SEM) to 2.7+/-0. 4 cm/s (P<0.05), probably reflecting loss of motion caused by tethering to apical segments. Volume loading increased myocardial Doppler velocities from 2.2+/-0.3 to 4.1+/-0.8 cm/s (P<0.05) and Doppler-derived strain from -12+/-1% to -22+/-2% (P<0.05), whereas peak LV elastance remained unchanged. CONCLUSIONS: Myocardial strain by Doppler echocardiography may represent a new, powerful method for quantifying regional myocardial function and is less influenced by tethering effects than Doppler tissue imaging. Like myocardial Doppler velocities, strain is markedly load-dependent.

Intracavitary filling pattern in the failing left ventricle assessed by color M-mode Doppler echocardiography.

OBJECTIVES: The present study aimed to investigate the mechanism of intracavitary changes in filling pattern during acute ischemic left ventricular failure and during beta-adrenergic blockade. BACKGROUND: Recent clinical studies with color M-mode Doppler imaging have shown abnormal intracavitary filling patterns in the diseased ventricle. METHODS: In open chest anesthetized dogs with intracardiac micromanometers and myocardial segment-length crystals, global ischemic left ventricular failure was induced (n = 8) by coronary microembolization. In nonischemic ventricles inotropy was decreased (n = 6) by intravenous propranolol and increased (n = 6) by intravenous isoproterenol. From color M-mode Doppler images we calculated the time difference between peak early diastolic filling velocity at the mitral tip and apex using computer analysis. The time difference of peak velocity was used as an index of the timing of apical filling. RESULTS: There was marked retardation of apical filling with microembolization and propranolol. Time difference of peak velocity increased from 20 +/- 6 (mean +/- SEM) to 101 +/- 17 ms (p < 0.05) and from 21 +/- 8 to 80 +/- 18 ms (p < 0.05), respectively. Time constant of isovolumic relaxation increased from 34 +/- 3 to 43 +/- 5 ms (p < 0.05) and from 31 +/- 1 to 39 +/- 3 ms (p < 0.05) during microembolization and beta-blockade, respectively. Isoproterenol tended to cause the opposite changes. Time difference of peak velocity showed a positive correlation with time constant of isovolumic relaxation (r = 0.89, p < 0.01) and a negative correlation with peak early transmitral pressure gradient (r = 0.88, p < 0.01). In the intact left ventricle, peak apical filling velocity coincided with peak early transmitral pressure gradient. During ischemic failure however, peak apical filling velocity occurred 53 +/- 14 ms after peak early transmitral pressure gradient had decreased to zero and at a time when transmitral flow had ceased, suggesting a change in intraventricular flow distribution. CONCLUSIONS: Color M-mode Doppler imaging revealed retarded apical filling during depression of myocardial function by global myocardial ischemia or beta-blockade. The abnormal filling pattern may be a sign of impaired left ventricular relaxation.

Juxtacardiac pleural pressure during positive end-expiratory pressure ventilation: an intraoperative study in patients with open pericardium.

OBJECTIVES: This study was conducted to measure the cardiac constraining effect of the lungs during positive end-expiratory pressure and relate extracardiac pleural pressure (radial stress) to airway pressure, right atrial pressure and left ventricular filling. BACKGROUND: During positive end-expiratory pressure ventilation, the extracardiac pressure is elevated, and therefore intracavitary filling pressure does not reflect ventricular preload. Estimates of this pressure might be useful clinically to assess left ventricular preload. METHODS: In eight patients who had undergone coronary or valvular surgery and whose pericardium was left widely open, a flat pleural balloon transducer was placed over the anterolateral left ventricular wall. We recorded pulmonary capillary wedge pressure, right atrial pressure and left ventricular short-axis end-diastolic area by transesophageal echocardiography. Incremental positive end-expiratory pressure was applied. RESULTS: Extracardiac pleural pressure increased (p < 0.01) from 0.6 +/- 1.8 (+/- SD) to 2.4 +/- 1.8, 5.3 +/- 1.5 and 8.2 +/- 1.5 mm Hg at a positive end-expiratory pressure of 5, 10 and 15 cm H2O, respectively. The slope relating extracardiac pleural pressure to positive end-expiratory pressure (in mm Hg) was 0.70 +/- 0.10, and the intercept was zero. Increasing extracardiac pleural pressure was associated with a progressive increase in pulmonary capillary wedge pressure and a decrease in left ventricular end-diastolic area. Consequently, although pulmonary capillary wedge pressure and left ventricular area changed in opposite directions, the value of pulmonary capillary wedge pressure minus extracardiac pleural pressure correlated positively with left ventricular area (r = 0.95, p < 0.001). Changes in right atrial pressure (Pra) correlated with changes in extracardiac pleural pressure (Ppleural): delta Pra = -0.3 + 0.56. delta Ppleural (r = 0.89, p < 0.001). CONCLUSIONS: In postoperative patients with open pericardium, pulmonary capillary wedge pressure minus extracardiac pleural pressure predicts left ventricular end-diastolic area during positive end-expiratory pressure. Further studies should be done to determine whether the observed relations between airway pressure and extracardiac pleural pressure and between right atrial pressure and extracardiac pleural pressure may give clinically useful estimates of left ventricular preload during positive end-expiratory pressure.

A potential clinical method for calculating transmural left ventricular filling pressure during positive end-expiratory pressure ventilation: an intraoperative study in humans.

OBJECTIVES: This study sought to investigate whether right atrial pressure could be used to estimate pericardial pressure during positive end-expiratory pressure (PEEP). BACKGROUND: Because of elevated intrathoracic pressure during PEEP, pulmonary capillary wedge pressure may not accurately reflect left ventricular preload. An estimate of pericardial pressure during PEEP would allow assessment of transmural filling pressure. METHODS: In eight patients, at the start of cardiac surgery, pericardial and pleural pressures were recorded by balloon transducers placed over the anterolateral left ventricular wall. We also recorded intravascular pressures and left ventricular short-axis area by transesophageal echocardiography. RESULTS: A stepwise increase in PEEP from 0 to 15 cm H2O caused a linear increase in pleural pressure from 0.3 +/- 0.6 (mean +/- SEM) to 6.1 +/- 0.8 mm Hg (p < 0.01). Pericardial pressure increased from 2.3 +/- 0.5 to 5.9 +/- 0.6 mm Hg (p < 0.01). The correlation between right atrial (Pra) and pericardial pressure (Pperic) was good: Pra = 0.85 x Pperic + 1.8, r = 0.77. The correlation between changes in right atrial pressure and in pericardial pressure was better: delta Pra = 0.96 x delta Pperic -0.2, r = 0.97. Pulmonary capillary wedge pressure increased with PEEP (p < 0.05), whereas left ventricular area decreased (p < 0.05). However, there was a progressive reduction in transmural pressure, calculated as wedge pressure minus pericardial pressure (p < 0.05), and in transmural pressure, estimated as wedge pressure minus right atrial pressure (p < 0.05). The estimated transmural filling pressure correlated (r = 0.86) with end-diastolic area. CONCLUSIONS: The present observations suggest that right atrial pressure may be used to estimate changes in pericardial pressure with PEEP and that pulmonary capillary wedge pressure minus right atrial pressure is a potentially clinically useful approximation of transmural filling pressure.

Assessment of pericardial constraint: the relation between right ventricular filling pressure and pericardial pressure measured after pericardiocentesis.

Experimental studies have shown that right ventricular filling pressure (that is, intracavitary diastolic pressure) approximates pericardial surface pressure but, in many patients after removal of pericardial effusion, right ventricular filling pressure has been found to markedly exceed pericardial pressure recorded by an open catheter. The aim of this study was to determine whether this apparent contradiction was related to the technique of pericardial pressure measurement. Nine patients with chronic pericardial effusion were studied and, although these pressures diverged to varying degrees in individual patients, the previous observation was confirmed in that, although initially similar, right ventricular filling pressure and pericardial pressure (measured by means of an open catheter) tended to diverge during removal of the effusate; when the evacuation was as complete as possible pericardial pressure was 2.1 +/- 1.0 (mean +/- SE), while right ventricular filling pressure was 8.7 +/- 1.7 mm Hg (p less than 0.01). In six open chest, anesthetized, volume-loaded dogs with pericardial effusion (50 ml), right ventricular filling pressure and pericardial pressures measured with both open catheter and flat balloon were all equal. With decreasing volume of pericardial fluid, right ventricular filling pressure and pericardial pressure (by catheter) diverged as had been observed in patients. However, pericardial pressure (balloon) continued to be equal to right ventricular filling pressure. (With 0 ml in the pericardium, right ventricular filling pressure = 12.9 +/- 0.9 mm Hg, pericardial pressure [catheter] = 1.4 +/- 1.9 mm Hg and pericardial pressure [balloon] = 12.4 +/- 1.5 mm Hg.) Thus, these observations support the use of right ventricular filling pressure as an estimate of pericardial constraint in patients.

Ventricular diastolic pressure-volume shifts during acute ischemic left ventricular failure in dogs.

Ischemic left ventricular failure was produced in eight acutely instrumented, anesthetized dogs to study the contribution of changing myocardial compliance and pericardial pressure to shifts in right and left ventricular diastolic pressure-volume relations. Right and left ventricular and pericardial volumes were measured by ungated computed tomography. Cardiac volumes were manipulated by infusion of saline solution, hemorrhage, phenylephrine infusion and, during failure only, nitroglycerin administration. During both control and failure periods, these interventions shifted the left and right ventricular pressure-volume relations by changing pericardial pressure only; that is, these interventions caused no change in the ventricular transmural pressure-volume relation. The induction of failure as such increased pericardial pressure only minimally and did not change the left ventricular or right ventricular transmural pressure-volume relations significantly. Volume loading during the control period caused an apparent pericardial creep which attenuated the pericardial effect on ventricular pressure-volume relations. During failure, volume loading caused an increase of right ventricular volume, but tended to decrease left ventricular volume; this was associated with a leftward displacement of the interventricular septum. In conclusion, in the presence of ischemic left ventricular failure as well as normally, changes in preload, afterload and circulating blood volume shift ventricular diastolic pressure-volume relations by stretching or relaxing the pericardium, thus changing pericardial pressure. In these circumstances, there were no consistent changes in myocardial compliance.

The pulmonary venous systolic flow pulse--its origin and relationship to left atrial pressure.

OBJECTIVES: The purpose of this study was to determine the origin of the pulmonary venous systolic flow pulse using wave-intensity analysis to separate forward- and backward-going waves. BACKGROUND: The mechanism of the pulmonary venous systolic flow pulse is unclear and could be a "suction effect" due to a fall in atrial pressure (backward-going wave) or a "pushing effect" due to forward-propagation of right ventricular (RV) pressure (forward-going wave). METHODS: In eight patients during coronary surgery, pulmonary venous flow (flow probe), velocity (microsensor) and pressure (micromanometer) were recorded. We calculated wave intensity (dP x dU) as change in pulmonary venous pressure (dP) times change in velocity (dU) at 5 ms intervals. When dP x dU > 0 there is a net forward-going wave and when dP x dU < 0 there is a net backward-going wave. RESULTS: Systolic pulmonary venous flow was biphasic. When flow accelerated in early systole (S1), pulmonary venous pressure was falling, and, therefore, dP x dU was negative, -0.6 +/- 0.2 (x +/- SE) W/m2, indicating a net backward-going wave. When flow accelerated in late systole (S2), pressure was rising, and, therefore, dP x dU was positive, 0.3 +/- 0.1 W/m2, indicating a net forward-going wave. CONCLUSIONS: Pulmonary venous flow acceleration in S1 was attributed to a net backward-going wave secondary to a fall in atrial pressure. However, flow acceleration in S2 was attributed to a net forward-going wave, consistent with propagation of the RV systolic pressure pulse across the lungs. Pulmonary vein systolic flow pattern, therefore, appears to be determined by right- as well as left-sided cardiac events.

Inosine infusion in dogs with acute ischaemic left ventricular failure: favourable effects on myocardial performance and metabolism.

Haemodynamic and metabolic effects of inosine were examined during acute left ventricular (LV) failure in closed-chest anaesthetised dogs. Embolisation of the left main coronary artery with 50 microm plastic microspheres induced severe depression of LV function, and the dogs remained in stable failure throughout the experimental period as shown in the untreated control dogs (n = 4). Intravenous infusion of inosine 3.8 to 7.5 mg . min-1 . kg-1 caused an increase in maximum LVdP/dt from 290 +/- 32 (mean +/- SEM, n = 8) to 376 +/- 39 kPa . s-1 and a decrease in LV end-diastolic pressure from 3.6 +/- 0.2 to 2.5 +/- 0.1 kPa. Total peripheral resistance decreased from 10.2 +/- 1.0 to 7.4 +/- 0.7 kPa . litre-1 min, and cardiac output increased from 1.64 +/- 0.17 to 2.27 +/- 0.23 litre . min-1 during inosine infusion. Myocardial blood flow increased from 65 +/- 10 to 94 +/- 16 cm3 . min-1 . 100 g-1 with no change in myocardial oxygen consumption. Inosine markedly decreased arterial concentrations and myocardial uptake of FFA. Arterial concentrations of glucose were moderately decreased while myocardial uptake of glucose showed a non-significant increase. Inosine markedly increased myocardial uptake of lactate. These metabolic changes were associated with increased plasma concentrations of insulin. In conclusion, inosine improved myocardial performance and increased myocardial uptake of carbohydrates relative to FFA during acute ischaemic LV failure in dogs.

Haemodynamic and metabolic effects of the antiarrhythmic drug melperone during acute left ventricular failure in dogs.

Haemodynamic and metabolic effects of the new antiarrhythmic drug melperone were studied during acute ischaemic left ventricular failure in closed-chest anaesthetized dogs. Embolisation of the left main coronary artery with 50 micrometer plastic microspheres induced severe depression of left ventricular performance as evidenced by a marked increase in left ventricular end-diastolic pressure and a marked reduction in the maximum rate of left ventricular pressure rise (LVdP/dtmax), cardiac output, and stroke volume. Six dogs received intravenous melperone 1.0 and 2.5 mg . kg-1 (cumulative dose) 90 and 115 min after the embolisation, respectively. Six other dogs received no treatment and served as controls. Melperone effected a marked reduction in left ventricular end-diastolic pressure, a slight but transient increase in LVdP/dtmax, a moderate reduction in heart rate, a moderate reduction in mean aortic blood pressure and total peripheral resistance and a moderate increase in stroke volume. Melperone moderately decreased myocardial O2-consumption, while myocardial lactate uptake remained unchanged. In conclusion, in contrast to commonly used antiarrhythmic drugs which may all induce cardiodepression, melperone improved left ventricular function in dogs with acute ischaemic left ventricular failure.

Changes in pulmonary vein flow pattern during volume loading.

OBJECTIVE: The aim was to investigate the effect of increased left ventricular filling pressure on the pulmonary vein flow (PVQ) pattern. METHODS: Pulmonary vein flow was recorded using an ultrasonic transit time flow meter in six anaesthetised dogs. Mean left atrial pressure was increased by stepwise volume loading from 7.8(SEM 1.3) to 18.9(1.9) mm Hg (p < 0.01). RESULTS: With loading the PVQ signal developed several characteristic positive and negative waves which corresponded to directionally opposite pressure waves in the left atrium. There was a marked increase in the amplitude of the PVQ signal: peak flow increased from 165(50) to 310(38) ml.min-1 (p < 0.01), while minimum flow decreased from 49(37) to -61(23) ml.min-1 (p < 0.01). The minimum value of PVQ occurred during early ventricular systole, corresponding to the left atrial C wave. With progressive loading there was an increasing deceleration of flow during atrial contraction. To quantify the effect of atrial contraction and the C wave on the flow pattern a ratio was calculated between the integrated flow from the start of atrial contraction to the nadir of the x descent and the integrated flow during the rest of the cardiac cycle. This ratio decreased from 0.40(0.06) to 0.11(0.07) with loading (p < 0.01). In each experiment this flow ratio varied inversely with mean left atrial pressure (regression coefficients between 0.66 and 0.97). CONCLUSIONS: Volume loading caused marked changes in the pulmonary vein flow pattern. The PVQ waves reflected the pressure waves in the left atrium. The relative flow during atrial contraction varied inversely with mean left atrial pressure. Further studies should be done to determine whether this index reflects left ventricular filling pressure under different conditions.

Increased cardiac expression of endothelin-1 mRNA in ischemic heart failure in rats.

OBJECTIVES: Plasma endothelin (ET) concentrations are increased in heart failure. The aims of the present study were to investigate to what extent cardiac ET mRNA expression is induced in ischemic heart failure and whether there may be compensatory downregulation of myocardial mRNA levels for the ETA and ETB receptor subtypes. METHODS: In rats with ischemic heart failure (left ventricular end-diastolic pressure > 15 mmHg) due to left coronary artery ligation. Northern blot analyses were performed on mRNA isolated from cardiac tissues. RESULTS: A substantial upregulation was revealed in all chambers of the failing hearts. Up to 27-fold upregulation (mean 10.6 +/- 4.0, P = 0.002) of left ventricular ET-1 mRNA levels was measured 1 week after myocardial infarction, whereas only a modest upregulation was detected after 6 weeks (mean 2.7 +/- 0.5, P < 0.05). Ribonuclease protection assay revealed 2.8 +/- 0.4-fold higher levels of ET-1 mRNA in the left ventricular area subjected to myocardial infarction compared to the non-infarcted tissue after 1 week. Left ventricular ET-1 mRNA correlated significantly with left ventricular end-diastolic pressure after 1 week (r2 = 0.86, P = 0.007). The ETA and ETB receptor mRNA levels tended to increase 1 week after myocardial infarction although these changes were not statistically significant. CONCLUSIONS: Cardiac ET-1 mRNA levels are increased in ischemic heart failure and correlate significantly with left ventricular end-diastolic pressure 1 week after myocardial infarction. The increase in cardiac ET-1 mRNA is not accompanied by a decrease in ET receptor mRNA.

Mechanism of action of nitrates. Role of changes in venous capacitance and in the left ventricular diastolic pressure-volume relation.

Nitroglycerin, when administered to patients with heart failure, causes a marked reduction in left ventricular filling pressure but often an increase in stroke volume and stroke work; based on the Frank-Starling principle, such a reduction in "preload" would be expected to result in a decrease in left ventricular end-diastolic volume and, therefore, a decline in stroke volume. Assessment of pressure-volume coordinates, however, has revealed that nitroglycerin produces a downward shift in the pressure-volume relationship. This apparent improvement in left ventricular compliance cannot be attributed to alterations in the elastic properties of the myocardium but rather appear to reflect a reduction in left ventricular external constraint. Recent animal and clinical investigations in our laboratory suggest that nitroglycerin causes venous dilatation (particularly in the mesenteric bed), thereby decreasing venous pressure at any given vascular volume. This decrease in cardiac filling pressure results in a decrease in heart size and, therefore, a reduction in pericardial pressure. Left ventricular transmural (intracavitary minus pericardial) pressure is little changed, however, so that end-diastolic volume and stroke volume are maintained.

Assessment of the splanchnic vascular capacity and capacitance using quantitative equilibrium blood-pool scintigraphy.

A series of human and animal experiments were carried out to assess the usefulness of equilibrium blood pool scintigraphy (EBPS) to study acute changes of the splanchnic vascular capacity and the splanchnic vascular pressure-volume (P-V) relationship. Corrected regional abdominal count rate changes, before and after various pharmacologic interventions, were used to assess regional splanchnic vascular volume changes. Animals were instrumented to manipulate and record splanchnic venous pressures. In patients, splanchnic vascular capacity increased by 5.2 +/- 6.9% (p less than 0.001) after 0.6 mg sublingual nitroglycerin while no significant change was noted after sugar pills (0.9 +/- 5.2%, p greater than 0.3). In dogs, splanchnic vascular capacity decreased by a mean of 16% during infusion of angiotensin (p less than 0.001) and increased by a mean of 32% during infusion of nitroprusside (p less than 0.001). The splanchnic vascular P-V curve was shifted rightwards during nitroglycerin administration. Thus, using the radionuclide technique we detected the expected qualitative and quantitative shifts in splanchnic capacity and capacitance. We conclude that EBPS is a useful method to assess acute changes of 1) the splanchnic vascular P-V relationship, in invasive animal studies, and 2) the splanchnic vascular capacity in noninvasive human and animal studies.

A mechanism for the nitroglycerin-induced downward shift of the left ventricular diastolic pressure-diameter relation.

Nitroglycerin has been shown to cause a downward shift in the left ventricular (LV) pressure-volume relation in patients. To test the hypothesis that this shift is mediated by an alteration in pericardial pressure, 13 patients undergoing diagnostic cardiac catheterization were studied. LV and right ventricular (RV) pressure (micromanometers) and LV diameter (2-dimensional echocardiography) were measured simultaneously before and after sublingual administration of 0.3 to 0.6 mg of nitroglycerin. In the 11 patients with hemodynamic effects from nitroglycerin, mean LV end-diastolic pressure decreased from 12.7 +/- 5 mm Hg (mean +/- standard deviation) to 7.3 +/- 3 mm Hg (p less than 0.002) and mean RV end-diastolic pressure declined from 7.7 +/- 3 mm Hg to 5.0 +/- 1 mm Hg (p less than 0.001). However, nitroglycerin caused only a slight (6%) reduction in LV minor axis diameter, from 52 +/- 8 mm to 49 +/- 9 mm (p less than 0.05). Diastolic pressure-diameter plots constructed from early and late diastolic measurements demonstrated a downward shift in the relation. However, when RV end-diastolic pressure was used as an estimate of pericardial pressure (a procedure validated by studies in our laboratory), the transmural pressure-diameter points before and after administration of nitroglycerin defined a single curve. These observations are in keeping with the conclusions that nitroglycerin did not alter the elastic properties of the myocardium and that the decrease in LV end-diastolic pressure induced by nitroglycerin was primarily attributable to a reduction in external constraint.

Selective positive end-expiratory pressure and cardiac function in dogs.

Effects of general (G) versus selective (S) right (R) and left (L) positive end-expiratory pressure (PEEP) were compared during differential lung ventilation in 11 anaesthetized dogs in the supine position. GPEEP 20 cmH2O decreased cardiac output (1 min-1) from 2.9 +/- 0.2 (mean +/- SE) to 1.7 +/- 0.5 (p less than 0.05), RPEEP from 2.8 +/- 0.2 to 2.2 +/- 0.2 (p less than 0.05) while LPEEP caused no significant change in cardiac output. GPEEP increased pleural pressure more than SPEEP. Pleural pressure was asymmetric during SPEEP. Both SPEEP and GPEEP increased pericardial pressure uniformly, but the increase was less marked with SPEEP. During GPEEP 20 cmH2O transmural left ventricular end-diastolic pressure (LVEDP) decreased markedly. SPEEP caused less marked reductions in transmural LVEDP. Qualitatively similar, but less marked changes were observed with PEEP 10 cmH2O. In conclusion, cardiac output decreased less with selective PEEP than with general PEEP. This was explained by less increase in pleural and pericardial pressure, and accordingly less decrease in LV transmural filling pressure.