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M J Aronovitz

Publications and source records attributed to M J Aronovitz.

27 records · Page 2Linked to original sources

Pulmonary artery structural changes in two colonies of rats with different sensitivity to chronic hypoxia.

Chronic hypoxia causes more severe pulmonary hypertension in the Hilltop colony of Sprague-Dawley rats than in the Madison colony and also greater polycythemia and vasoconstriction. This study examines the structural features of the pulmonary artery bed, another contributing factor to hypoxic hypertension. After 14 days of hypobaric hypoxia, in Hilltop rats, more of the intraacinar arteries became muscular, and the medial thickness of intraacinar and preacinar arteries was greater. In Hilltop control rats, muscle was found in more intraacinar arteries, but, paradoxically, acute hypoxic vasoconstriction was less. Thus, while in chronic hypoxia increased muscle correlates with pulmonary hypertension, in control rats the reserve seems to be true. The increased muscle in control Hilltop rats could, however, predispose to the greater muscularization seen after chronic hypoxia.

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Effects of chronic in utero hypoxemia on rat neonatal pulmonary arterial structure.

Idiopathic persistent pulmonary hypertension of the newborn infant (PPHN) is characterized by intrauterine structural remodeling of the pulmonary arterial bed, consisting of precocious development of muscle in intraacinar arteries, proliferation of adventitial connective tissue, and sometimes medial hypertrophy of preacinar arteries. To evaluate whether gestational hypoxemia causes these changes, we studied pulmonary arterial structure in two groups of newborn rats: one control, the other exposed to hypoxemia produced by maternal hypoxia during the second half of gestation. Morphometric analysis of the pulmonary arterial bed was performed after barium injection into the pulmonary arteries and formol saline expansion of the air spaces. Birth weight was similar in each group. Hematocrit was elevated in the hypoxemia group (51% +/- 1.0% vs 46% +/- 0.8%, P less than 0.005). The structure of preacinar and intraacinar arteries was similar and normal in both groups. Chronic fetal hypoxemia in the rat does not produce the pulmonary arterial structural changes identified in fatal cases of PPHN in human infants.

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Effect of amrinone on right ventricular function: predominance of afterload reduction.

Although the bipyridine agent amrinone is reported to have a positive inotropic effect on the left ventricle, the effect of this drug on right ventricular contractility in the clinical setting is unknown. We studied the effect of short-term intravenous administration of amrinone on right ventricular systolic function in nine patients with severe congestive heart failure and, using radionuclide ventriculography, examined the right ventricular end-systolic pressure-volume relationship to determine whether reduced right ventricular afterload or increased contractility predominantly accounted for the observed improvement in right ventricular systolic function. In each patient the right ventricular end-systolic pressure-volume relationship was derived with use of varying doses of nitroprusside. After nitroprusside was stopped, intravenous amrinone (3 mg/kg) caused decreases from baseline in pulmonary arterial end-systolic pressure in eight of nine patients (23 +/- 11% [overall mean +/- SE], p less than .05), and in pulmonary vascular resistance in all patients (38 +/- 6%, p less than .001). Right ventricular end-systolic volume decreased (23 +/- 8%, p less than .01) and right ventricular ejection fraction increased (31 +/- 10%, p = .01). The amrinone-induced decrease in right ventricular end-systolic volume was compared with that predicted for right ventricular afterload reduction alone based on the effect of amrinone on pulmonary arterial end-systolic pressure and the pressure-volume relationship observed during infusion of nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effects of chronic in utero hypoxia on the pulmonary vasculature of the newborn guinea pig.

This report analyzes the effect on pulmonary vascular structure and function in the newborn guinea pig of chronic fetal hypoxemia, induced by maternal hypobaric hypoxia (380-420 torr) without direct interference with the utero-placental blood flow. Six pregnant guinea pigs were maintained in hypobaric chambers, 10 newborns from their litters being the hypoxic group. Twenty newborns from the litters of 10 pregnant guinea pigs maintained in air were the control group. After spontaneous delivery catheters were placed in the left carotid and the main pulmonary arteries of the newborns. Oxygen consumption was measured, pressures recorded from the pulmonary artery, right ventricle, and right atrium, oxygen saturation and hemoglobin concentration estimated on blood from systemic arteries, pulmonary artery, and right atrium, and cardiac output calculated (Fick principle). All data were normalized per kilogram body weight. Morphometric analysis of the pulmonary vasculature after injection of the pulmonary arteries showed no difference between the groups. Contrary to expectation chronic hypoxemia in utero did not cause pulmonary hypertension or the precocious muscularization of the precapillary unit found in human cases of persistent pulmonary hypertension: it caused growth retardation, a feature not typical of the human syndrome.

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Changes in pulmonary blood flow affect vascular response to chronic hypoxia in rats.

We banded the left pulmonary artery in rats to investigate, in the same animal, the effect of both increased and decreased flow on the lung vasculature and to determine how these hemodynamic states modify the structural changes produced by a 2-week exposure to hypobaric hypoxia. In unanesthetized rats, pressures were recorded from the main pulmonary artery and aorta via indwelling catheters, cardiac output was calculated by the Fick principle, and pulmonary and systemic vascular resistance estimated. Technetium-99m macroaggregated albumin was injected and radionuclide activity counted separately over the right and left lungs as a measure of flow. At postmortem, right and left ventricles of the heart were weighed and the lungs injected to permit analysis of arteriograms and morphometric assessment of structural changes in the pulmonary vascular bed. Flow in the left lung was reduced to one-fifth normal in rats with left pulmonary artery bands. In "room air" rats, pressure proximal to the left pulmonary artery band and in the right lung was slightly higher than in nonbanded controls, but not as high as in nonbanded or banded hypoxic rats. Changes in flow and pressure in both lungs of "room air" rats with left pulmonary artery bands were associated with a mild degree of extension of muscle into peripheral pulmonary arteries normally nonmuscular, medial hypertrophy of normally muscular arteries, and reduced arterial density. These three structural changes were present in both lungs of "hypoxic" rats but were much more severe. High flow in the right lungs of "hypoxic rats" with left pulmonary artery bands worsened only the degree of extension. Decreased flow and pressure in the left lungs of these animals prevented both the extension and the medial hypertrophy of hypoxia, but not the severe reduction in arterial density. It seems that the latter may occur as a direct response to low oxygen tension, whereas extension and medial hypertrophy are influenced by altered flow and pressure, respectively.

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Successful placement and re-expansion of a new balloon expandable stent to maintain patency of the ductus arteriosus in a newborn animal model.

OBJECTIVE: We performed this study in order to evaluate the usefulness of a new balloon expandable stent for maintaining ductal patency in a neonatal piglet model and to evaluate the ability to re-expand the stent weeks following initial implantation. BACKGROUND: Maintaining patency of the ductus arteriosus without administration of Prostaglandin E has been reported previously using balloon dilation and stent implantation techniques. However, the experience is limited and the currently available stents are not modified for neonates. METHODS: 14 newborn piglets all at age 12 days and median weight 3.6 Kg (range 2.7-4.3 Kg), underwent initial balloon dilation of the ductus arteriosus. Angiography after dilation demonstrated no significant left to right shunt. All piglets underwent successful stent (3.5 mm x 17 mm) placement in the ductus arteriosus. RESULTS: Percutaneous ductal stent implantation via the arterial route was successful in all piglets with angiographic demonstration of a significant left to right shunt. Follow-up studies at weekly intervals with color flow Doppler were used to confirm patency of the stents. In 3 piglets the stent was not patent at initial follow-up and autopsy revealed sub-optimal stent placement. In two animals the stent was later re-expanded to 4 mm at 22 days, in one to 4 mm at 30 days and in one to 6 mm at 15 days, maintaining flow for an additional period of 15 to 34 days.(ABSTRACT TRUNCATED AT 250 WORDS)

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A new low profile balloon atrial septostomy catheter: initial animal and clinical experience.

OBJECTIVE: To evaluate the safety and efficacy of a new low profile balloon septostomy catheter in neonatal animals as well as in one newborn infant. BACKGROUND: Balloon atrial septostomy remains one of the most commonly performed palliative procedures in pediatric cardiology. The currently available septostomy catheter requires a large introducer sheath (6 or 7F), does not have an end hole for confirmation of position or pressure measurement and is limited in patients with a small left atrium due to its large balloon inflated diameter. METHODS: Four neonatal piglets (average weight 3.9 kg) underwent percutaneous balloon atrial septostomy using the new balloon catheter inflated to 1 cc via a 5F sheath in the femoral vein. Two other piglets (average weight 4.9 kg) underwent septostomy with the conventional catheter inflated to 3.5 cc via a 6 or 7F sheath in the femoral vein. All animals underwent transthoracic echocardiography pre and post septostomy. All animals were sacrificed after the procedure and the size of the atrial defect created was measured. One neonate with Taussig-Bing anomaly underwent septostomy with the new balloon catheter. RESULTS: The left atrium was entered in all piglets. It was easier to enter the left atrium with an end hole catheter which was exchanged over a wire with the septostomy catheter. Septostomy was performed with the new or conventional catheters without complications. Echocardiography demonstrated a very small patent foramen ovale prior to the procedure and a large atrial defect after septostomy. The average size of the defect created by the new catheter was 11.3 x 10 mm in diameter and 11 x 10 mm using the conventional catheter. A 10 x 10 mm atrial communication was created in the neonate. CONCLUSIONS: This study demonstrates the safety and efficacy of this new catheter. This catheter will be of potential importance in patients with a small left atrium and in small neonates with congenital heart disease requiring septostomy.

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Magnetic resonance imaging in ischemic injury after heart transplantation in rats.

Magnetic resonance imaging with and without gadolinium (Gd)-DTPA has been shown to enable detection of coronary occlusive ischemic injury and heart transplant rejection. This study was performed to examine findings on magnetic resonance images associated with ischemic injury after heart transplantation in rats. Magnetic resonance imaging was performed immediately before death in 22 rats, between 1 and 90 days after isogeneic (Lewis grafts, Lewis host; or Fischer graft, Fischer host) heterotopic heart transplantation. Ischemic injury, characterized histologically by cellular infiltration or myocyte necrosis, correlated inversely with graft duration. It was graded as moderate to severe in 5 of 5 rats killed at 1 to 2 days, and in 0 of 9 animals killed at greater than or equal to 30 days. T2-weighted myocardial signal intensity (TR = 2.3 seconds; TE = 90 milliseconds) correlated inversely with graft duration and was significantly greater in grafts with moderate or severe histologic abnormalities than in grafts with absent or minimal changes. GD-DTPA-induced myocardial enhancement was judged on T1-weighted images (TR = 0.5 seconds, TE = 25 milliseconds). Areas of intense enhancement were present in all seven grafts with severe histologic abnormalities, but in only 3 of 15 grafts with absent to moderate histologic abnormalities. In conclusion, after heart transplantation in rats, ischemic injury causes increased T2-weighted signal intensity and Gd-DTPA-induced T1-weighted signal enhancement--findings similar to those described in transient coronary occlusive ischemia and in graft rejection. Abnormalities seen on magnetic resonance images during the first few posttransplant weeks may represent ischemic injury rather than rejection.

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Total lymphoid irradiation and discordant cardiac xenografts.

Total lymphoid irradiation can prolong concordant cardiac xenografts. The effects of total lymphoid irradiation in a discordant xenograft model (guinea pig to rat) were studied with and without adjuvant pharmacologic immunosuppression. Inbred Lewis rats were randomly allocated to one of four groups. Group 1 (n = 6) served as a control group and rats received no immunosuppression. Group 2 (n = 5) received triple-drug therapy that consisted of intraperitoneal azathioprine (2 mg/kg), cyclosporine (20 mg/kg), and methylprednisolone (1 mg/kg) for 1 week before transplantation. Group 3 animals (n = 5) received 15 Gy of total lymphoid irradiation in 12 divided doses over a 3-week period. Group 4 (n = 6) received both triple-drug therapy and total lymphoid irradiation as described for groups 2 and 3. Complement-dependent cytotoxicity assay was performed to determine if a correlation between complement-dependent cytotoxicity and rejection-free interval existed. Rejection was defined as cessation of graft pulsation and was confirmed by histologic test results. Only groups 1 and 2 showed a difference in survival (group 1, 6.9 +/- 1.0 minutes; group 2, 14.2 +/- 2.7 minutes, p = 0.02). Although total lymphoid irradiation did decrease complement-dependent cytotoxicity, linear regression revealed no correlation between complement-dependent cytotoxicity and graft survival (coefficient of correlation, 0.30). Unlike concordant cardiac xenografts, total lymphoid irradiation with or without triple-drug therapy does not prolong graft survival.

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