Drugs in pregnancy: Implications for a cardiologist.

The safe use of drugs during pregnancy depends on several factors including the time of application, the type of drug and its dose. In the present review, the effect of certain therapeutic drugs on pregnancy is first described using general principles, followed by a more focused discussion on the type of adverse effects related to specific cardiovascular drugs used during pregnancy. In particular, adverse events related to the use of antihypertensive and antiarrhythmic drugs and anticoagulants are described, followed by the characterization of congenital cardiovascular defects resulting from the use of various drugs during pregnancy.

ANG II type 1 receptor antagonist irbesartan inhibits coronary angiogenesis stimulated by chronic intermittent hypoxia in neonatal rats.

Chronic hypoxia has been shown to stimulate myocardial microvascular growth and improve cardiac ischemic tolerance in young and adult rats. The aim of this study was to determine whether the ANG II type 1 receptor (AT(1)) pathway was involved in these processes. Newborn Wistar rats, exposed to chronic intermittent hypoxia (8 h/day) for 10 days, were simultaneously treated with AT(1) receptor blocker irbesartan and compared with untreated animals.

Verification of coronary angiogenesis by quantitative morphology.

The angiogenic response may be reliably evaluated only by the methods of quantitative morphology. These methods may appear deceivingly simple but they contain several possible pitfalls. This review presents major principles of proper methodology for determination of tissue vascularization using quantitative morphology.

Cardiac function, microvascular structure, and capillary hematocrit in hearts of polycythemic rats.

The effect of polycythemia on the coronary microcirculation was studied in young male rats. Two experimental models of polycythemia were employed: cobalt-induced polycythemia, which mimics hypoxia-induced changes, and erythropoietin-induced polycythemia, which circumvents these changes. In both models, baseline left ventricular function was normal, whereas maximal systolic and developed pressures were decreased.

Effect of anemia on cardiac function, microvascular structure, and capillary hematocrit in rat hearts.

The effect of anemia on the coronary microcirculation was studied in young male rats. Chronic anemia resulted in increased left ventricular end-diastolic pressure and decreased functional reserve. Cardiac mass in anemic animals increased by 25%.

The effect of treatment with low dose ACE inhibitor and/or diuretic on coronary microvasculature in stroke-prone spontaneously hypertensive rats.

Angiotensin II is considered to have angiogenic properties. Nevertheless, several authors reported an increase in coronary capillary density after treatment with ACE inhibitors. The aim of the present study was to evaluate the effect of treatment with low doses of ACE inhibitor perindopril, low doses of the diuretic indapamide, or a combination of the two on microvascular structure in hearts from stroke-prone spontaneously hypertensive rats (SHR-sp).

Effects of chronic heparin administration on coronary vascular adaptation to hypertension and ventricular hypertrophy in sheep.

Background: Hypertension decreases myocardial perfusion capacity in adults for several reasons, including insufficient coronary angiogenesis with left ventricular (LV) hypertrophy, arteriolar hypertrophy, and altered vasomotion. Heparin influences growth factors that promote angiogenesis and vasodilation and inhibit arteriolar wall thickening.

Methods And Results: Adult sheep were given heparin 200 U/kg body wt SC twice daily throughout 6 weeks of LV and coronary hypertension from a progressively constricted ascending aortic band (n=14).

Pressure overload induced in newborn rats: effects on left ventricular growth, morphology, and function.

Gradual pressure overload was induced by abdominal aortic constriction in male rats on postnatal d 6 (AC6) or 2 (AC2). At the age of 8 wk, the systemic blood pressure was measured, and the contractile performance of the left ventricle (LV) was assessed after acute ligation of the ascending aorta in open chest anesthetized animals. The LV free wall was used for the determination of collagen concentration and morphometric analysis of cardiac myocytes and capillaries.

The role of diltiazem in treating hypertension and coronary artery disease: new approaches to preventing first events.

Objective: To review the role of diltiazem in treating and preventing a group of cardiovascular diseases, including painful and silent cardiac ischemia, stroke, nonfatal myocardial infarction and sudden cardiac death, by modulating certain physiological causes that they appear to share.

Data Sources: A MEDLINE search was conducted for all clinical articles on the use of diltiazem for hypertension and coronary artery disease. When clinical data were not available, basic research findings were reviewed.

Transplantation-induced atrophy of normal and hypertrophic rat hearts: effect on cardiac myocytes and capillaries.

Changes in tissue structure of hearts undergoing atrophy following heterotopic isotransplantation were studied. Both normal and hypertrophic hearts were used, originating from male and female rats. Aortic constriction produced in newborn rats, resulted in an 86 and 155% increase of left ventricular mass in male and female rats, respectively.

Geometry of the capillary net in human hearts.

The geometry of the coronary capillary bed in human hearts was studied using samples obtained during cardiac surgery of children operated for tetralogy of Fallot and samples from fresh normal hearts used for valve harvesting. The results revealed a similar coronary capillary density and heterogeneity of capillary spacing in samples from both groups. A double-staining method was used to distinguish between capillary segments close to the feeding arteriole (proximal capillaries) and segments distant from the arteriole (distal capillaries).

Early and late effect of neonatal hypo- and hyperthyroidism on coronary capillary geometry and long-term heart function in rat.

Objective: The aim of the present study was two-fold: (1) to examine the effect of hyper- and hypothyroidism on the developing coronary capillary network in neonatal rats, and (2) to determine in adult rats that had re-established euthyroid status whether long-term changes in capillary geometry or cardiac function had been induced by either neonatal thyroid condition.

Method: Two-day-old rats were treated every other day for 12 or 28 days with either 3,3'5-triiodo-l-thyronine or 0.05% 6-n-propylthiouracil.

Short- and long-term effects of neonatal hypo- and hyperthyroidism on coronary arterioles in rat.

Neonatal hypo- and hyperthyroid effects on coronary arteriolar geometry were examined in newborn male Sprague-Dawley rats treated for 12 or 28 days with either triiodothyronine or propylthiouracil. Long-term effects were assessed in weaned rats 52 days after stopping treatment. Influence of both neonatal conditions was more pronounced after 28 days.

Immediate postnatal rat heart development modified by abdominal aortic banding: analysis of gene expression.

Proliferative growth of the ventricular myocyte (cardiomyocyte) is primarily limited to embryonic, fetal and very early neonatal periods of heart development. In contrast, cardiomyocyte maturation, as evidenced by cellular hypertrophy, is a long-term process that can occupy the bulk of the life-span of the mature organism. As the newborn myocyte undergoes a 'transition' from proliferative to hypertrophic growth, ventricular remodeling of the non-myocyte compartment is characterized by increased extracellular matrix (ECM) formation and coronary capillary angiogenesis.

Red blood cell spacing in rat coronary capillaries during the cardiac cycle.

Theoretical studies have demonstrated a pronounced effect of red blood cell (RBC) spacing on tissue oxygen supply. Our objective was to collect data regarding RBC spacing and related linear capillary hematocrit (Hct) in rat coronary capillaries, from two distinct locations within the capillary bed (proximal and distal portions), in the subendo- and midmyocardium, during systole and diastole. Hearts were rapidly frozen in situ, and tissue sections were stained in order to distinguish capillaries in proximal and distal portions of the capillary bed, as well as the RBCs within them.

The effect of AT1 receptor antagonist on chronic cardiac response to coronary artery ligation in rats.

Objective: The aim was to study the effect of the AT1 receptor antagonist losartan on hemodynamic and morphometric changes following experimental infarction.

Methods: Experimental infarction was produced in adult male rats by ligating the coronary artery. Treatment with losartan was compared to untreated controls, in rats with experimental infarction and sham-operated animals.

Transmural channels can protect ischemic tissue. Assessment of long-term myocardial response to laser- and needle-made channels.

Background: We previously found that transmural laser channels failed to acutely increase myocardial blood flow. Nevertheless, this method is being used to treat patients with coronary artery disease who are unable to undergo angioplasty or bypass graft surgery and in cases in which previous surgery has failed. To reconcile the lack of an acute increase in blood flow with beneficial effects claimed in patients, our hypothesis was that the channel-making process might, over time, stimulate a protective effect, possibly by the growth of new vessels linking channels to the existing circulation.

Changes in calcium handling in atrophic heterotopically isotransplanted rat hearts.

Atrophy of the rat heart induced by hemodynamic unloading after heterotopic transplantation is associated with impaired relaxation while systolic function remains normal when compared to the heart of the recipient animal. To identify possible underlying mechanisms for the above, we studied some aspects of membrane calcium handling using postextrasystolic potentiation of contractions in the isolated right ventricular papillary muscle and in the left ventricle of the Langendorff-perfused heart. We also compared the alterations of the unloaded heart with those of overloaded hypertrophic hearts of rats with suprarenal aortic constriction.

Proliferating cell nuclear antigen (PCNA) detection of cellular proliferation in hypothyroid and hyperthyroid rat hearts.

Immunocytochemical techniques examining the expression of cell proliferation-related markers such as proliferating cell nuclear antigen (PCNA), may be employed to provide visual and quantitative evidence of cell proliferation. The efficacy of this method in frozen samples was tested on sections of 2-day-old rat heart. Mouse monoclonal anti-PCNA and goat anti-mouse IgG2a peroxidase-conjugated antibodies were applied to tissue cross-sections.