Kenneth P. Brin

Arterial hemodynamics in human hypertension.

Differences in aortic impedance between normotensives and hypertensives are not well characterized. We examined impedance in 8 normotensive and 11 hypertensive (mean 96.7 vs. 122.2 mmHg) age-matched, Chinese patients undergoing cardiac catheterization at rest, during nitroprusside, and handgrip exercise before and after beta blockade (propranolol). Hypertensives had higher resistance (2,295 vs. 1713 dyn-s/cm5), characteristic impedance (145.7 vs. 93.9 dyn-s/cm5), total external power (1,579 vs. 1174 mW), peripheral reflections (ratio of backward to forward wave components of 0.54 vs. 0.44), and first zero crossing of impedance phase angle (4.15 vs. 2.97 Hz). These abnormalities were eliminated with vasodilatation. Differences between groups were not further exacerbated when pressure was increased during handgrip exercise. Beta blockade further increased resistance and reflections. Thus, hemodynamic abnormalities of essential hypertension (increased resistance, reflections, and pulse wave velocity, and decreased compliance) are compatible with an increased vasomotor tone that is further unmasked during generalized beta blockade.

Augmentation of regional coronary blood flow by intra-aortic balloon counterpulsation in patients with unstable angina.

Intra-aortic balloon counterpulsation is capable of reducing afterload in patients with unstable angina. Whether it is also capable of augmenting coronary blood flow to poststenotic myocardium is controversial. We studied seven patients receiving maximal drug therapy and requiring balloon pumping for unstable angina as balloon volume and assist ratio were altered. All patients had greater than 90% stenosis of the proximal left anterior descending coronary artery. With maximal augmentation (40 cc balloon volume, 1:1 assist ratio) great cardiac vein flow, representing the efflux from the left anterior descending coronary artery bed, rose from a baseline of 52 +/- 20 to 67 +/- 25 ml/min (mean +/- SD, p = .004) and mean aortic diastolic pressure increased from 77 +/- 13 to 99 +/- 33 mm Hg (p = .004). Increased great cardiac vein flow correlated with increased mean aortic diastolic pressure across changes in balloon volumes (off, 20 cc, 30 cc, and 40 cc) and changes in assist ratio (off, 1:4, 1:2, and 1:1) (p = .02). However, the intermediate balloon volumes produced great cardiac vein flows at an intermediate level between full assist and no assist (p less than .05), whereas the intermediate assist ratios did not augment flow. Thus balloon pumping increased flow to a bed fed by collateral vessels or critical stenoses; this increased flow correlated with increased aortic diastolic pressure, indicating probable loss of autoregulatory ability.

Regional wall motion improvement after coronary thrombolysis with recombinant tissue plasminogen activator: Importance of coronary angioplasty

To evaluate functional recovery in 20 consecutive patients with acute myocardial infarction who received recombinant tissue-type plasminogen activator, serial two-dimensional echocardiograms were performed before and immediately after tissue plasminogen activator administration and at 1 and 10 days postinfarction. Tissue plasminogen activator was administered intravenously (17 patients) or by intracoronary infusion (3 patients) after angiographic confirmation of total occlusion. Reperfusion, documented by angiography, occurred in 13 of the 20 patients. The mean time from onset of chest pain to thrombolysis was 5.1 +/- 1.1 hours. Echocardiograms were evaluated for regional function with a visual semiquantitative scoring system by two independent observers who had no knowledge of patient identity, temporal sequence, therapy or effect of therapy. There was no immediate or 24 hour improvement in wall motion. At day 10 compared with pretreatment, 28 of 33 reperfused infarct zone segments versus 6 of 20 nonreperfused infarct segments demonstrated improved wall motion (p = 0.01). This improvement did not relate to time from onset of chest pain to successful thrombolysis. Of reperfused infarct zone segments in the distribution of coronary artery balloon dilation, 19 of 23 segments exhibited improvement versus 7 of 17 (reperfused, no angioplasty) and 6 of 20 (nonreperfused, no angioplasty) segments (p = 0.001). Infarct zone segments reperfused at the time of ongoing chest pain demonstrated functional recovery compared with segments reperfused in the absence of chest pain (18 of 23 versus 10 of 20, respectively; p = 0.05). Thus, in this uncontrolled series, there was echocardiographically detectable improvement in function of reperfused infarct segments 10 days after coronary thrombolysis with recombinant tissue plasminogen activator.

Arterial hemodynamic indexes in Marfan's syndrome.

Aortic impedance, wave reflection magnitude, and compliance were measured in patients with Marfans syndrome during diagnostic cardiac catheterization. Impedance and wave reflections were calculated from standard Fourier series analysis of ascending aorta micromanometer pressure and electromagnetic flow records. Compliance was estimated by a method recently proposed that uses the area under the pressure-time curve assuming a two-element Windkessel model of the circulation. Measurements were made in the baseline state, during vasodilatation with nitroprusside, after beta-adrenergic receptor blockade with intravenous propranolol, and during vasodilatation after beta-blockade. Marfans syndrome produces alterations from normal in some hemodynamic variables: during baseline conditions, the magnitude of wave reflection was higher than in normal patients. This was normalized by vasodilatation and further increased by beta-blockade. Despite the greatly dilated aortic root, the aortic characteristic impedance was in the normal range, suggesting increased aortic wall stiffness. The baseline total arterial compliance was greatly increased with nitroprusside and was reduced by beta-blockade. beta-Blockade did not decrease the maximum acceleration of blood into the ascending aorta. These are the first detailed measurements of hemodynamic indexes in this disease. The results suggest that acute beta-blockade is not necessarily beneficial in reducing hemodynamic loading on an already dilated aortic root.

Effect of nitroprusside on hydraulic vascular loads on the right and left ventricle of patients with heart failure.

We studied the effect of nitroprusside on the hydraulic vascular load of the right and left ventricle in seven patients with severe left ventricular failure. At doses of 0.25–0.75,μg/kg/min, stroke volume increased progressively from 40.1 to 48.6 ml and left ventricular end-diastolic pressure decreased from 24.5 to 11.2 mm Hg. Accompanying this improvement in left ventricular performance were doserelated decreases in mean ventricular pressures, pulmonic and systemic resistances and the lower-frequency components of input impedance moduli. Characteristic impedance and both total and oscillatory external power were decreased in the pulmonic, but not the aortic, vasculature. In this class of patients, right ventricular unloading is a striking and direct effect of nitroprusside and may account, in part, for imnproved left ventricular performance through ventricular interdependence.

Aortic impedance and hydraulic power in the chick embryo from stages 18 to 29.

Little is known about the hemodynamic properties of the rapidly expanding arterial bed during embryonic development. Using a servo-null pressure system and 20-MHz pulsed Doppler velocity meter, we recorded simultaneous dorsal aortic pressure and velocity waveforms. The waveforms were digitized at 3-msec intervals and subjected to Fourier analysis. We calculated hydraulic energy and the impedance spectrum to 10 Hz. From stages 18 to 29, heart rate (148±3 to 193±9 beats/min), systolic pressure (1.14±0.12 to 3.04±0.10 mm Hg), and mean dorsal aortic blood flow (21 ±2 to 214±19 mm3/min) increased. Peripheral vascular resistance (Z0: 30.4±4.8 to 6.4±0.7 dyneXsec/mm5), and the impedance moduli (Z1: 6.5±1.0 to 1.7±0.2 dyneYsec/mm5; Z2:6.1±1.2 to 1.7±0.1 dyneXsec/mm5; Z3: 7.3±1.1 to 1.7±0.2 dyneXsec/mm5) decreased. Total hydraulic power increased from 48±7 to 2,606±96 nW, while the proportion of oscillatory energy increased from 29±2percent; to 65±4percent;. With development hydraulic load decreases, total external work increases and the dorsal aorta and embryonic vascular bed becomes more compliant. A greater proportion of total energy is expanded in pulsatile blood flow, suggesting that ventricular-arterial coupling is less efficient later in development.

Effect of nitroprusside on wave reflections in patients with heart failure

The relationship between wave reflections and ventricular-vascular coupling has been the subject of considerable speculation. Since we have previously shown that low-dose nitroprusside infusion improved ventricular-vascular coupling (as evidenced by increases in cardiac output and in aortic and pulmonary arterial total external power) in patients with severe left ventricular failure and secondary pulmonary hypertension, we chose to examine the changes in their aortic and pulmonary arterial wave reflections in this study. Wave reflection indexes examined included [1] calculated backward and forward pressure waves and the ratio of their magnitudes (reflection factor), [2] the reflection coefficient spectrum obtained by taking the ratios of the corresponding Fourier harmonics of the backward and forward waves, [3] two terminal reflection coefficients calculated as Γt=(R-Zc)/R+Zc) where Z is characteristic impedance and R is either total resistance or vascular resistance, and [4] the difference between the maximum and minimum impedance moduli for frequencies of 4 to 15 Hz. In the systemic vasculature, nitroprusside produced large reductions in the elevated vascular resistances and decreased aortic reflections as indexed by the reflection factor and by both terminal reflection coefficients. In contrast, however, no significant changes were found in the pulmonary artery wave reflection indexes despite large reductions in the pulmonary resistances.

Effects of left ventricular loading by negative intrathoracic pressure in dogs.

There are many factors, both intrinsic and extrinsic to the left ventricle, that can affect its function when negative intrathoracic pressure is imposed. In this study, we examined whether the left ventricular response to the afterload imposed by negative intrathoracic pressure was similar to that imposed by partial aortic constriction. We used steady-state right heart bypass to control pulmonary venous return to the left ventricle and reflex blockade to maintain constant heart rate and contractility. To impose negative intrathoracic pressure we used a pressure chamber fitted over a midsternal thoracotomy, which allowed steady negative pressure to be applied to all intrathoracic surfaces. Left ventricular volumes were measured from biplane cineradiograms of multiple 1-mm markers implanted in the left ventricular mldwall. With cardiac output and heart rate constant, we compared the left ventricular response to two different levels of negative intrathoracic pressure and to increasing aortic pressure by partial aortic constriction. In each case, negative intrathoracic pressure produced a rise in the left ventricular end-systolic and end-diastolic volumes as well as transmural pressures similar to the effects of partial aortic occlusion. Thus, when cardiac output, heart rate, and contractility are maintained constant and all external restraints on the left ventricle are removed, the left ventricle responds in a similar manner to an increase in hydraulic load whether produced by a decrease in intrathoracic pressure or by partial aortic occlusion.

Estimation of Arterial Compliance

As has been demonstrated in several previous chapters, the Windkessel model of the arterial system, despite its simplicity and attendant limitations, continues to be extremely useful both for understanding vascular physiology and for investigating ventricular/vascular coupling. The important parameters of this model are the compliance and the peripheral resistance. Whereas calculation of total peripheral resistance is straightforward and estimates are easily obtainable in vivo, estimation of total arterial compliance (the increment in volume produced by an increment of pressure) is very difficult. Direct measurement of overall arterial compliance is complicated by the need to measure accurately total arterial blood volume, and has been accomplished only in experimental animals (Shoukas and Sagawa 1973). Therefore in most instances, estimates of compliance are made indirectly by assuming that the aortic diastolic pressure decays exponentially with a time constant that is the product of total arterial resistance and compliance (Bourgeois et al. 1974; Conroy 1969; Defares and Van der Waal 1969, 1973; Deswysen, Charlier, and Gevers 1980; Iriuchijima, Kumazawa, and Kawakami 1971; Levy, Birkui, and Saumont 1978; Levy et al. 1985; Messerli, Frohlich, and Nutura 1985; Randall, Van den Bos, and Westerhof 1984; Simon et al. 1979; Simon, Levenson, and Safar 1985; Ventura et al. 1984).

Use of negative intrathoracic pressure to obtain end-systolic pressure volume relations in dogs

Left ventricular contractility can be assessed from the end-systolic pressure-volume relationship (ESPVR). In this study we test the hypothesis that the same ESPVR can be obtained by varying LV loading with different levels of negative intrathoracic pressure as by varying LV filling. In six dogs mean aortic transmural pressure was used to approximate LV end-systolic pressure and LV volume was determined from data gathered from biplane cineradiograms of multiple markers placed in the LV midwall. In each preparation right heart bypass allowed control of cardiac output while the thoracic pressure was varied with a box surrounding a midsternal thoracotomy. Reflex effects were minimized by ganglionic blockade and bilateral vagotomy. ESPVRs were obtained by varying the cardiac output at constant thoracic pressure or by changing intrathoracic pressure at constant cardiac output. The slopes of the ESPVRs were not significantly different. This result implies that LV loading by negative intrathoracic pressure, in this highly controlled preparation, can be used to generate a systolic LV elastance similar to that obtained by varying LV filling.