Right Ventricular Myocardial Blood Flow Research Articles

Abstract 15033: Chronic Thromboembolic Pulmonary Hypertension Patients Have Reduced Bi-Ventricular Myocardial Perfusion Reserve, Which Improves Following Pulmonary Thromboendarterectomy

Introduction: This study seeks to determine whether bi-ventricular myocardial perfusion reserve (MPR) is reduced in patients with chronic thromboembolic pulmonary hypertension (CTEPH) compared to a control group using quantitative myocardial perfusion MRI. Methods: We prospectively enrolled 4 CTEPH patients (55±14 years, 4 males) and performed stress-rest (10 min apart) protocol using our 5-fold accelerated radial perfusion sequence. In one patient, we repeated stress-rest perfusion acquisition following pulmonary thromboendarterectomy (PTE). As a control group, we retrospectively identified 8 subjects (49±12 years, 5 males) with no evidence of vascular late gadolinium enhancement or perfusion defects who underwent a similar stress-rest protocol. The pixel-wise stress-rest myocardial blood flow (MBF) maps and MPR were quantified for both the left ventricular (LV) and right ventricular (RV) free walls. Two sample t-test was used to compare between the CTEPH and control groups. Results: Figure 1a shows representative stress and rest MBF maps and the corresponding MPR values comparing a CTEPH patient and a control subject. Summarizing the results of all patients (Figure 1b), compared to the control group, the CTEPH group had significantly (p < 0.05) lower stress LV MBF (1.56 ± 0.34 vs. 2.66 ± 0.50 ml/g/min), RV MBF (1.48 ± 0.19 vs. 2.56 ± 0.53 ml/g/min), LV MPR (1.65 ± 0.43 vs. 2.32 ± 0.50), and RV MPR (1.59±0.46 vs. 2.50 ± 0.53), but non-significant difference (p > 0.05) in resting LV MBF (0.96 ± 0.12 vs. 1.21 ± 0.43 ml/g/min) and RV MBF (0.96 ± 0.14 vs. 1.07 ± 0.36 ml/g/min). In one patient, PTE improved RV MPR from 1.43 to 2.49 as well as LV MPR from 1.24 to 2.36. Conclusions: This study suggests that both RV and LV MPR are reduced in CTEPH patients compared with controls and that PTE may improve RV as well as LV MPR in CTEPH patients. Future studies include additional enrollment of CTEPH patients, determining the diagnostic and prognostic role of RV and LV MPR in the context of PTE.

Abstract 13798: Obstructive Sleep Apnea Severity and Abnormal Right Ventricular Flow Reserve in Adult OSA Patients Who Received Rubidium-82 Cardiac PET Perfusion Imaging

Background: Obstructive sleep apnea (OSA) is associated with right ventricular (RV) remodeling, RV dysfunction and pulmonary hypertension. Myocardial flow reserve (MFR), the ratio of stress-to-rest myocardial blood flow (MBF), is an index of coronary microvascular health. Recent evidence suggests that severe OSA is associated with abnormal left ventricular MFR (LVFR). However, little is known about MFR in the RV of patients with OSA. In this study we examined the relationship between measures of OSA severity and RV MFR (RVFR) in humans. Methods: We conducted RV MBF assessment in 47 persons with OSA who had a cardiac positron emission tomographic (PET) perfusion scan. All participants had in-laboratory polysomnography. RVFR <2.0 was chosen as threshold for abnormal RVFR to coincide with the 25 th percentile of RVFR in our sample. Abnormal LVFR was also defined as <2.0 based on thresholds from previously determined studies. We compared the mean apnea-hypopnea index (AHI), oxygen desaturation index (ODI) and time spent with <90% oxygen saturation (T90%). Results: The mean age of the participants was 58 years and 63% were female. There was a strong correlation between RVFR and LVFR (Spearman Rho = 0.63, P<0.001). The mean AHI was greater among persons with RVFR <2 compared to those with RVFR≥2 [mean (SE) AHI: 63 (20) v. 32 (5), P=0.042]. This trend was observed with the ODI although it was not statistically significant. Given the RVFR and LVFR were strongly correlated, we created a ratio of RVFR to LVFR to account for the LV MBF. The mean AHI and ODI among persons with RVFR/LVFR <1 was greater than those with ≥1; p = 0.025 and p=0.031 respectively. See the figure for more details. Conclusion In patients with OSA, patients with reduced RVFR had higher AHI and ODI indicating greater severity of OSA. The exact mechanism behind this phenomenon is not known. Future studies should further characterize the relationship between RV myocardial blood flow and OSA.

Interrelation between ventricular function, myocardial blood flow, and O2 consumption changes at birth in lambs.

We studied the interrelation of changes in ventricular external work, myocardial blood flow, and O2 consumption at birth. Eleven fetal sheep were instrumented under general anesthesia at 133-134 days gestation with arterial, peripheral venous, and left atrial catheters, and in five fetuses, a catheter was also inserted into the coronary sinus. Fetal left ventricular (LV) and right ventricular (RV) outputs and myocardial blood flows (radioactive microspheres), hemodynamics, and LV O2 consumption were measured 1 wk later. Fetuses were delivered by cesarean section, and measurements were repeated 1 and 4 h after birth. RV minute work (mmHg.l.kg-1) was greater in fetuses (10.8 +/- 0.5 vs. 15.6 +/- 1.0 P < 0.001), but because of increased LV minute work (to 20.9 +/- 1.4, P < 0.005) and unchanged RV minute work, this pattern was reversed by 1 h after birth. RV myocardial blood flow (ml.min-1.100 g-1) was predominant in fetuses (234 +/- 25 vs. 306 +/- 27, P < 0.001), but this also reversed in lambs; this reversal was related to unchanged 1-h (248 +/- 16) and lower 4-h LV myocardial blood flow (199 +/- 9, P < 0.05) and a progressive fall in RV myocardial blood flow (1 h: 245 +/- 20, P < 0.05; 4 h: 174 +/- 12, P < 0.005). LV O2 consumption (ml.min-1.100 g-1) increased between fetal (8.1 +/- 0.6) and 1-h lambs (18.9 +/- 1.3, P < 0.005) because of a rise in the LV arteriovenous O2 content difference (3.6 +/- 0.4 vs. 7.5 +/- 0.6 ml/dl, P < 0.005). External work performed per unit myocardial blood flow (mmHg.l.ml-1) in the LV increased between fetal and 1-h lambs (1.92 +/- 0.14 to 3.33 +/- 0.15, P < 0.001) and, in the RV, between fetal and 4-h lambs (2.09 +/- 0.18 to 2.92 +/- 0.24, P < 0.01). The proportion of consumed O2 converted to external work was, however, similar in fetal (34.6 +/- 3.1%) and 1-h (31.3 +/- 2.9%) and 4-h lambs (34.5 +/- 3.6%). These findings indicate that 1) a switch from a fetal RV to a newborn LV dominance is due to increased LV pumping performance, 2) an associated switch in LV and RV myocardial blood flow patterns is mainly related to a fall in RV myocardial blood flow, 3) a postnatal rise in LV O2 consumption results from enhanced LV arteriovenous O2 extraction, not increased LV myocardial blood flow, 4) ventricular external work per unit myocardial blood flow increases postnatally, particularly in the LV, and 5) LV mechanical efficiency is not altered after birth.

Right ventricular pressure overload during acute lung injury: Cardiac mechanics and the pathophysiology of right ventricular systolic dysfunction

Right ventricular (RV) pressure overload (PO) accompanying acute lung injury is associated with a poor prognosis. To determine if RV ischemia (RVI) is responsible for RV failure (RVF) during acute PO induced by an acute lung injury, a group of eight dogs was studied with the pericardia open after instrumentation with RV, left ventricular (LV), and pulmonary artery (PA) Millar catheters, a PA thermodilution catheter, an aortic fluid-filled catheter, and RV and LV septal-free wall segment length crystals. The animals were studied during baseline, and after infusing glass beads into the right atrium sufficient to first double the PA pressure (PAP), then triple the PAP, and finally to produce RVF (decreased cardiac output with increased RV preload). Transmural RV biopsies were obtained at each phase for adenosine triphosphate and creatine phosphate (CP) assays. To determine the mechanism of RVI, a second group of nine dogs was studied (with the pericardia closed) at baseline, after a doubling of PAP and during RVF. Right ventricular myocardial blood flow was determined by a microsphere technique at each phase and was correlated with the determinants of RV myocardial O 2 demand and supply. In the open pericardia group, RVF, but not doubling or tripling of PAP, was associated with a decrease in CP to 50% of baseline conditions, confirming RVI (4.82 ± 3.67 versus 10.39 ± 3.94 μmol/gm wet weight; P < .005). In the closed pericardia group, RV myocardial blood flow increased in response to myocardial O 2 demands (multiple R = .69 for endocardial and .64 for epicardial flow; P < .05), although the ratio for total RV blood flow to myocardial O 2 demand ratio (planimetered area beneath RV pressure tracing) decreased (4.88 ± 2.76 versus 2.08 ± 2.14; P < .05). In both groups of dogs, RVF was associated with a similar decrease in LV end diastolic segment length or preload (17% in open group and 10% in closed group; P = NS between groups) and stroke work. From these observations, we conclude that after an acute lung injury, RVPO induces RVF because RV myocardial O 2 demand outstrips RV myocardial O 2 supply. Coincidentally with RVF, LV function is depressed on a preload-mediated basis independent of the pericardium, suggesting a dominant “series” interaction between both ventricles. These observations suggest that therapy in patients with acute lung injury is better aimed at increasing RV myocardial blood flow and RV function.

Preload Dependence of Right Ventricular Blood How: I. The Normal Right Ventricle

Right ventricular (RV) failure is commonly treated with intravascular volume expansion to increase the RV–left atrial pressure gradient and improve left-sided filling. As RV pressure rises, chamber distention occurs and wall tension increases. These studies were designed to determine if increased wall tension might impede RV myocardial blood flow in the normal canine right ventricle and thus contribute to RV failure. Hemodynamic data, the septal–RV free wall dimension, and RV myocardial blood flow were obtained at low and high levels of preload and in both the autoregulated and vasodilated (adenosine, 2 mg per kilogram of body weight per minute) states. Elevated filling pressure decreased RV myocardial blood flow in both the autoregulated (0.85 ± 0.18 to 0.67 ± 0.15 ml/min/gm; p < .05) and vasodilated (2.25 ± 0.50 to 0.85 ± 0.25 ml/min/gm; p < .05) states but did not change the transmural distribution of blood flow to the right ventricle. Vasodilator reserve was markedly impaired in the high-preload state. These observations suggest that preload is an important determinant of RV myocardial blood flow. Volume loading to treat RV dysfunction may be limited by impairment of RV myocardial blood flow.

Regional myocardial blood flow and coronary vascular reserve in unanesthetized young calves exposed to a simulated altitude of 3500 m for 8--10 weeks.

We determined regional myocardial blood flow (15-micrometer tracer microspheres) and hemodynamics in nine normal calves, seven calves with right ventricular (RV) hypertrophy induced by pulmonary artery banding (PAB) at sea level, and five calves exposed to simulated high altitude (HA) of 3,500 m (PB = 500 mm Hg) for 8--10 weeks. Progression of RV hypertrophy was very rapid in HA calves. RV weight:body weight ratio of 2.74 +/- 0.20 g/kg at 8--10 weeks of sojourn at HA significantly exceeded that in PAB calves (1.98 +/- 0.11 g/kg) 20 weeks post-banding. All calves were studied unanesthetized at sea level before (control) and during maximal coronary vasodilation (iv adenosine; 4 microM/kg per min). Normal and HA calves were also studied during acute hypoxemia (PaO2: 42 +/- 1 mm Hg) induced by administration of 12--13% O2 + N2 in the inhaled gas. RV myocardial blood flow was significantly increased only in PAB calves, whereas in HA calves it was similar to that in normal calves. Left ventricular (LV) mass and blood flow were identical in three groups of calves. Polycythemia did not occur in HA calves. Minimal coronary vascular resistance per unit weight of the hypertrophied RV was identical to that in the normal RV myocardium. This suggested that, despite very fast progression of RV hypertrophy in HA calves, functional cross-sectional area of the RV coronary vascular bed kept pace with the increase in cardiac mass. Minimal coronary vascular resistance per unit weight of the left ventricular myocardium was also identical in three groups of calves. This suggested that chronic hypoxemia by itself did not cause an increase in the functional cross-sectional area of the LV coronary vascular bed. Acute hypoxemia resulted in a significant increase in myocardial blood flow in all calves, but in HA calves, RV endo:epi perfusion ratio decreased below 1.00. Transmural RV myocardial blood flow and RV systolic pressure in HA calves during acute hypoxemia significantly exceeded that in normal calves.

Regional myocardial blood flow and coronary vasodilator reserve during acute right ventricular failure due to pressure overload in swine

Right ventricular (RV) failure due to acute RV pressure overload has been attributed to the inability of RV myocardial blood flow to increase following maximal RV coronary vasodilatation, which may occur with mild to moderate RV systolic hypertension, such that further increments in RV systolic pressure by way of decreasing RV coronary driving pressure hamper RV myocardial perfusion. To test this hypothesis, myocardial blood flow (15-μm-diameter tracer microspheres) was studied during adenosine infusion (3 μmole · kg −1 · min −1) instituted before and during acute RV failure in 10 closed-chest ketamine anesthetized young pigs. Acute RV failure, characterized by 10 mm Hg increase in RV end-diastolic pressure, 15 mm Hg drop in mean aortic pressure and 30% drop in cardiac output, was produced by partial constriction of the main pulmonary artery upon inflation of a previously implanted cuff. Acute RV failure was accompanied by a significant increase in myocardial blood flow in the RV free wall (91%) and right side of the septum (44%) while left ventricular myocardial blood flow was unaltered. Adenosine infusion during acute RV failure resulted in a significant increase in ventricular myocardial blood flow despite a significant drop in mean aortic pressure while RV end-diastolic and RV systolic pressures were further increased. Thus, the concept of maximal RV coronary vasodilatation during acute RV failure was not supported by these data. RV myocardial blood flow with adenosine infusion during acute RV failure (3.8 ml.min −1 · g −1) was, however, only 67% of that observed without RV failure (5.7 ml.min −1 · g −1). Also, during acute RV failure + adenosine, RV endo:epi flow ratio decreased markedly. We believe these differences were due to a combination of factors, namely, decreased diastolic duration for RV perfusion consequent upon prolongation of RV systole due to RV pressure overload, and higher back pressure opposing the diastolic RV perfusion because of significantly elevated preload.

Blood flow in the hypertrophied right ventricular myocardium of unanesthetized ponies.

To examine the effects of right ventricular (RV) hypertrophy on regional myocardial blood flow and coronary vascular reserve, hemodynamics and myocardial blood flow (15-micrometers radio-nuclide-labeled microspheres) were studied in 12 unanesthetized adult ponies before and during intravenous isoproterenol HCl infusion (1 microgram.kg-1.min-1). Six ponies served as controls, whereas in each of the others the main pulmonary artery (PA) had been banded 35-90 days prior to the study. Marked RV hypertrophy was present in PA-banded animals. In these ponies, there was a significant increase in RV systolic pressure (147%), heart rate (88%), RV tension-time index (279%), and RV myocardial blood flow (137%), while their RV coronary vascular resistance was only 40% of that for control ponies. Blood flow in right side of the interventricular septum was also significantly higher in the PA-banded ponies. Endo/epi perfusion ratio exceeded 1.00 for both ventricular freewalls in all animals. With isoproterenol infusion, there was a marked increase in myocardial blood flow in both groups. However, in PA-banded ponies the endo/epi flow ratio decreased precipitously below 1.00 in both ventricular freewalls. In control ponies this did not happen in the RV freewall, and RV coronary vascular resistance decreased to 19% of its control value. In PA-banded ponies, the magnitude of decline in RV coronary vascular resistance was much smaller, only 32% of that for control ponies. It is concluded that, unlike in LV hypertrophy, transmural myocardial blood flow per unit mass is much higher in the hypertrophied RV myocardium of adult resting ponies, and this higher RV perfusion occurs at the expense of curtailed RV coronary vascular reserve.

Regional coronary blood flow and coronary vascular reserve in unanesthetized calves at rest and during pharmacologic stress

The present study was carried out: (a) To determine whether the uniformity of transmural left ventricular (LV) myocardial blood flow (MBF) is due to a gradient of vasoactive tone or to a gradient of vascularity favoring the deeper layers. (b) To examine the changes in right ventricular (RV) MBF and coronary vascular reserve of conscious calves brought about by various kinds of stress. Hemodynamics and MBF (15-μm tracer microspheres) were studied in six awake calves before and during maximal coronary vasodilatation induced by adenosine infusion (4 μ M/kg/min). Although heart rate increased by 46% and mean aortic blood pressure decreased by 29% with adenosine infusion, the RV and LV MBF had increased by 710 and 394%, respectively. Thus under basal conditions we found RV coronary vascular reserve to be greater than that in the LV. The endo:epi ratio during maximal coronary vasodilatation did not decrease below 1.00 in both ventricles. This suggested that normally higher LV subendocardial perfusion (i.e., endo:epi > 1.0) of resting awake calves is most likely not due to a out → in diminishing gradient of vasomotor tone. Minimal coronary vascular resistance was identical for both ventricles. MBF was also studied in six additional calves at control, during isoproterenol infusion (0.2 μg/kg/min), pacing, and acute volume overload before and after propranolol pretreatment. The percentage increase in RV MBF per unit weight was higher than that in the LV MBF with each stress. With isoproterenol stress, LV endo:epi had decreased significantly below 1.0 while RV endo:epi was well maintained. Propranolol pretreatment significantly blunted the increase in RV and LV MBF brought about by acute volume overload.

The pathophysiology of failure in acute right ventricular hypertension: hemodynamic and biochemical correlations.

Acute right ventricular (RV) hypertension and failure occur clinically. In this study we examined the mechanism of RV failure. Adult dogs were studied acutely under anesthesia; dogs were instrumented for measurement of pressures and right coronary artery blood flow. Myocardial blood flow and cardiac output were determined with radionuclide-labeled microspheres, and the presence of ischemia was determined by biochemical analysis of ventricular biopsies. RV hypertension was produced by constricting the pulmonary artery and was increased until RV failure occurred, as evidenced by decreased aortic pressure and cardiac output and increased RV end-diastolic pressure. With increasing RV systolic pressure, RV myocardial blood flow failed to increase in proportion to demand. At the onset of RV failure, there was no reactive hyperemia of right coronary flow compared with control, indicating the absence of further coronary vascular reserve; biochemical analysis demonstrated that the RV free wall was ischemic; the LV free wall was not. Infusion of phenylephrine raised aortic pressure and hence, myocardial perfusion pressure; RV failure reversed as shown by decreased RV end-diastolic pressure and increased cardiac output and RV systolic pressure; reactive hyperemia of right coronary flow was restored and the biochemical indexes of ischemia were reversed, demonstrating that ischemia is the cause of failure in acute RV hypertension.