Long-Term Outcomes of Bovine versus Porcine Mitral Valve Replacement: A Multicenter Analysis.

Introduction: Recent national guidelines recommending mitral valve replacement (MVR) for severe secondary mitral regurgitation have resulted in an increased utilization of mitral bioprosthesis. There is a paucity of data on how longitudinal clinical outcomes vary by prosthesis type. We examined long-term survival and risk of reoperation between patients having bovine vs. porcine MVR. Study Design. A retrospective analysis of MVR or MVR + coronary artery bypass graft (CABG) from 2001 to 2017 among seven hospitals reporting to a prospectively maintained clinical registry was conducted. The analytic cohort included 1,284 patients undergoing MVR (801 bovine and 483 porcine). Baseline comorbidities were balanced using 1 : 1 propensity score matching with 432 patients in each group. The primary end point was all-cause mortality. Secondary end points included in-hospital morbidity, 30-day mortality, length of stay, and risk of reoperation. Results: In the overall cohort, patients receiving porcine valves were more likely to have diabetes (19% bovine vs. 29% porcine; p < 0.001), COPD (20% bovine vs. 27% porcine; p=0.008), dialysis or creatinine >2 mg/dL (4% bovine vs. 7% porcine; p=0.03), and coronary artery disease (65% bovine vs. 77% porcine; p < 0.001). There was no difference in stroke, acute kidney injury, mediastinitis, pneumonia, length of stay, in-hospital morbidity, or 30-day mortality. In the overall cohort, there was a difference in long-term survival (porcine HR 1.17 (95% CI: 1.00-1.37; p=050)). However, there was no difference in reoperation (porcine HR 0.56 (95% CI: 0.23-1.32; p=0.185)). In the propensity-matched cohort, patients were matched on all baseline characteristics. There was no difference in postoperative complications or in-hospital morbidity and 30-day mortality. After 1 : 1 propensity score matching, there was no difference in long-term survival (porcine HR 0.97 (95% CI: 0.81-1.17; p=0.756)) or risk of reoperation (porcine HR 0.54 (95% CI: 0.20-1.47; p=0.225)). Conclusions: In this multicenter analysis of patients undergoing bioprosthetic MVR, there was no difference in perioperative complications and risk of reoperation of long-term survival after matching.

Role of sex hormones in development of chronic mountain sickness in rats.

After chronic exposure to hypoxia, Hilltop Sprague-Dawley rats developed excessive polycythemia and severe pulmonary hypertension and right ventricular (RV) hypertrophy, signs consistent with human chronic mountain sickness; however, there were gender differences in the magnitude of the polycythemia and susceptibility to the fatal consequence of chronic mountain sickness. Orchiectomy and ovariectomy were performed to evaluate the role of sex hormones in the gender differences in these hypoxic responses. After 40 days of exposure to simulated high altitude (5,500 m; barometric pressure of 370 Torr and inspired Po2 of 73 Torr), both sham-gonadectomized male and female rats developed polycythemia and had increased RV peak systolic pressure and RV hypertrophy. The hematocrit was slightly but significantly higher in males than in females. Orchiectomy did not affect these hypoxic responses, although total ventricular weight was less in the castrated high-altitude rats. At high altitude, the mortality rates were 67% in the sham-operated male rats and 50% in the castrated animals. In contrast, ovariectomy aggravated the high-altitude-associated polycythemia and increased RV peak systolic pressure and RV weight compared with the sham-operated high-altitude female rats. Both sham-operated control and ovariectomized females suffered negligible mortality at high altitude. The present study demonstrated that 1) the male sex hormones play no role in the development of the excessive polycythemia, pulmonary hypertension, and RV hypertrophy during chronic hypoxic exposure or in the associated high mortality and 2) the female sex hormones suppressed both the polycythemic and cardiopulmonary responses in vivo during chronic hypoxic exposure.

Possible role of pulmonary blood volume in chronic hypoxic pulmonary hypertension.

Chronic hypoxia increases the total blood volume (TBV) and pulmonary arterial blood pressure (Ppa) and induces pulmonary vascular remodeling. The present study was undertaken to assess how the pulmonary blood volume (PBV) changes during hypoxia and the possible role of PBV in chronic hypoxic pulmonary hypertension. A novel method has been developed to measure the TBV, PBV, and Ppa in conscious rats. The method consists of chronic implantation of a loose ligature around the ascending aorta and pulmonary artery, so that when the ligature is drawn tightly, it traps the blood in the pulmonary vessels and left heart and simultaneously kills the rat. The pulmonary veins are then ligated to separate the left ventricular blood volume from the PBV. This surgical approach, together with chronic catheterization of the pulmonary artery and the use of 51Cr-labeled red blood cells, allows measurement of TBV, PBV, and Ppa. This method has been used to analyze the relationships between TBV and PBV and between Ppa or right ventricular hypertrophy and PBV in two rat strains with markedly different TBV and Ppa responses to chronic hypoxia. PBV per given lung weight did not increase and even decreased during hypoxia despite marked increases in TBV. There was a close correlation between Ppa or right ventricular hypertrophy and PBV in the two strains of chronically hypoxic animals, suggesting that a greater PBV plays a significant role in the development of severe chronic hypoxic pulmonary hypertension in the altitude-susceptible Hilltop rats.

Chronically instrumented rat model for hemodynamic studies of both pulmonary and systemic circulations.

We developed a chronic rat preparation in which a flow probe is placed around the ascending aorta and arterial catheters are implanted in the systemic and pulmonary circulations. This preparation was used to continuously monitor cardiac output (CO), systemic arterial pressure (Psa), and pulmonary arterial pressure (Ppa). More than 80% of the instrumented animals appeared healthy and continued to gain weight for longer than 2 wk. Stable CO, Psa, and Ppa were observed throughout this period. The effects of angiotensin II and hypoxia on the systemic and pulmonary circulations were studied, and possible adverse effects on the heart of long-term implantation of the flow probe were examined. This rat model provides a physiological small-animal preparation for short- and long-term hemodynamic and therapeutic studies on both the systemic and pulmonary circulations.

Hemodynamic effects of glucagon after acute mesenteric ischemia in rats.

We have previously shown that iv glucagon improved survival in rats from 33 to 83% when given after, but not during, superior mesenteric artery (SMA) occlusion. This study investigated potential hemodynamic mechanisms of this effect. In Part 1, cardiac output (CO) was measured in 12 male Sprague-Dawley rats with an electromagnetic flow-probe that had been placed around the ascending aorta 5 days previously. Under pentobarbital anesthesia, the SMA was occluded for 85 min. All rats received normal saline (NS, 15 ml/kg/hr) for 1 hr before and after SMA declamping. Control rats (n = 6) received only NS. Treated rats (n = 6) received NS plus glucagon (1.6 micrograms/kg/min iv) for 1 hr postocclusion. CO decreased 50% during the first hour after SMA declamping in control rats, but only 11% in glucagon-treated rats (P less than 0.02). Systemic vascular resistance (SVR) increased by 90% in control rats by 1 hr after declamp, but only 9% in glucagon rats (P less than 0.04). Systemic blood pressure and heart rate were not different in the two groups. In Part 2, relative distribution of visceral blood flow was measured with radiolabeled microspheres injected in the aortic root before clamping, before declamping, and 1 hr postdeclamping in 10 rats (5 glucagon, 5 control) using the above protocol. After SMA clamping, the proportion of visceral blood flow distributed to the intestine fell from 45 to 20% (P less than 0.05). During reperfusion, the proportion of intestinal flow exceeded baseline (P less than 0.05), but was not different in control (64%) and glucagon-treated rats (56%).(ABSTRACT TRUNCATED AT 250 WORDS)

Does atrial natriuretic factor protect against right ventricular overload? I. Hemodynamic study.

We studied the effects of synthetic atrial natriuretic factor (ANF, 28-amino acid peptide) on base-line perfusion pressures and pressor responses to hypoxia and angiotensin II (ANG II) in isolated rat lungs and on the following hemodynamic and renal parameters in awake, chronically instrumented rats: cardiac output (CO), systemic (Rsa) and pulmonary (Rpa) vascular resistances, ANG II- and hypoxia (10.5% O2)-induced changes in Rsa and Rpa, and urine output. Intra-arterial ANF injections lowered base-line perfusion pressures and blunted hypoxia- and ANG II-induced pressor responses in the isolated lungs. Bolus intravenous injection of ANF (10 micrograms/kg) into intact rats decreased CO and arterial blood pressures of both systemic and pulmonary circulations and increased Rsa. ANG II (0.4 micrograms/kg) increased both Rsa and Rpa, and hypoxia increased Rpa alone in the intact rats. ANF (10 micrograms/kg) inhibited both ANG II- and hypoxia-induced increases in Rpa but did not significantly affect the ANG II-induced increase in Rsa. The antagonistic effect of ANF on pulmonary vasoconstriction was reversible and dose-dependent. The threshold doses of ANF required to inhibit pulmonary vasoconstriction were in the same range as those required to elicit diuresis and natriuresis. The data demonstrate that ANF has a preferential relaxant effect on pulmonary vessels constricted by hypoxia or ANG II. Both the renal and the pulmonary vascular effects of ANF may represent fundamental physiological actions of ANF. These actions may serve as a negative feedback control system that protects the right ventricle from excessive mechanical loads.

Does atrial natriuretic factor protect against right ventricular overload? II. Tissue binding.

Previous studies have led us to hypothesize that the physiological significance of the diuretic and pulmonary vaso-relaxant effects of atrial natriuretic factor (ANF) is to protect the right heart. This study was designed to evaluate the relative importance of various peripheral tissues as sites of ANF action by tracing the temporal pattern of distribution of 125I-ANF and quantitating the specific binding sites. An in vivo approach, utilizing trace amount of 125I-ANF was adopted to simulate physiological conditions. 125I-ANF injected either intravenously or intra-arterially was quickly bound to peripheral tissues with less than 5% remaining in the circulation after 1 min. The relative binding capacity was greatest in the lung, followed by the kidney, right ventricle, adrenal gland, and left ventricle. The magnitude of specific ANF binding sites per gram of tissue weight followed a similar order. The data demonstrate that ANF released under all circumstances is quickly bound to the target organs, particularly the lung and the kidney, and suggest that these two organs could be the most important target organs of ANF. This evidence provides further support for the proposed hypothesis that a major evolutionary role of ANF is the protection of the right ventricle from mechanical loads.

Reticulocytosis, increased mean red cell volume, and greater blood viscosity in altitude susceptible compared to altitude resistant rats.

We have identified two strains (H and M) of Sprague-Dawley rat with markedly different susceptibilities and cardiopulmonary responses to chronic hypobaria. To further characterize factors responsible for these differing cardiopulmonary responses to chronic hypobaria, the present study examined differences in hematologic responses between the strains and assessed the contribution of differences in blood viscosity to differences in pulmonary vascular resistance. Following a 4-5 week exposure to simulated high altitude (0.5 atm), hemoglobin, hematocrit, mean red cell volume, and reticulocyte count were all increased in the susceptible H compared to the resistant M rats, whereas red blood cell counts were similar. Sea level controls manifested no differences. Blood viscosity, measured in a capillary viscometer, was 53% greater in chronically hypoxic H than in M rats, and plasma viscosities were similar. Blood from high altitude H rats increased pulmonary vascular resistance more than blood from high altitude M rats when perfused into lungs isolated from high altitude rats of either strain. In conclusion, high altitude H rats have an increased population of immature red cells, leading to a greater mean red cell volume and hematocrit than in high altitude M rats. These hematologic differences contribute to the the increased blood viscosity and greater pulmonary vascular resistance of H compared to M rats after 4 weeks' high altitude exposure.

Acute and chronic pulmonary pressor responses to hypoxia: the role of blunting in acclimatization.

We studied two strains of Sprague-Dawley rats: the Madison (M) that acclimatizes successfully to high altitude; and the Hilltop (H), that manifests signs of chronic mountain sickness at high altitude and has a high mortality rate. Awake, chronically instrumented animals were tested at sea level, at intervals during 30 days at a simulated altitude of 5500 m, and during 10 to 15 days of recovery at sea level. Mean pulmonary artery pressure (PAP) rose at high altitude to reach 60 mm Hg in H and 40 mm Hg in M, but the acute pressor response to hypoxia at sea level was much more pronounced in M than H. Depression of PAP by normoxic exposures in H rats at high altitude was slightly early in the period of stay but was enhanced with further prolongation of high altitude residence. The M rats, in contrast, had a blunted response (normoxia had very little depressant effect on PAP) after the first 24 h at high altitude, and it remained so for the duration of the stay. On return to sea level the response of H rats remained unchanged for 7 days, but the blunted response of the M rats at high altitude reversed at sea level to become exaggerated. We conclude: that responses of PAP to acute hypoxia do not forecast what the chronic response will be; that the appearance of an unidentified mechanism during chronic hypoxia in the M strain attenuates the vasoreactivity of the pulmonary vessels to hypoxia; and that the absence of such a blunting mechanism in H leads to the higher PAP in this strain and its morbid consequences. The hypothesis is put forward that the existence of such a blunting mechanism is an important factor in the adaptability of species to high altitude.