Cardiovascular responses to hemorrhage during acute and chronic hypoxia

Previous work from our laboratory had demonstrated attenuation of systemic vasoreactivity to pressor agents in rats after acute or chronic exposure to hypoxia. Therefore we hypothesized that hemorrhage of acutely hypoxic (12% O2) or chronically hypoxic (barometric pressure 380 mmHg for 3 wk) rats would deter the normal increase in total peripheral resistance (TPR) and thus decrease the ability to maintain blood pressure. Progressive hemorrhage (2% of blood volume per min) was performed under conditions of either normoxia or acute hypoxia in conscious rats. In control animals, the increase in TPR observed during normoxic hemorrhage was absent when hemorrhage was performed in acute hypoxia. Furthermore, the amount of blood removal required to achieve hypotension was reduced under conditions of acute hypoxia. In contrast, chronically hypoxic rats exhibited no difference in the threshold for hypotension between conditions of acute normoxia and hypoxia and demonstrated an increased hypotensive threshold under both normoxic and hypoxic conditions compared with control animals. We next hypothesized that the prolonged threshold for hypotension observed in chronically hypoxic rats might be due to hypoxia-induced right ventricular hypertrophy. Such ventricular hypertrophy may minimize stimulation of ventricular volume receptors thought to elicit the reflex fall in heart rate and TPR occurring in extreme underfill conditions. Therefore we compared the cardiovascular responses to hemorrhage in rats with right ventricular hypertrophy resulting from administration of monocrotaline with those from rats treated with vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

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Chronic propranolol treatment blunts right ventricular hypertrophy in rats at high altitude

Journal of Applied Physiology ◽

10.1152/jappl.1980.48.3.473 ◽

1980 ◽

Vol 48 (3) ◽

pp. 473-478 ◽

Cited By ~ 15

Author(s):

N. F. Voelkel ◽

I. F. McMurtry ◽

J. T. Reeves

Keyword(s):

Right Ventricular ◽

High Altitude ◽

Ventricular Hypertrophy ◽

Pressor Response ◽

Acute Hypoxia ◽

Right Ventricular Hypertrophy ◽

Receptor Blockade ◽

Beta Receptor ◽

Propranolol Treatment ◽

Beta Receptor Blockade

Chronic beta-receptor blockade has been reported to inhibit right ventricular hypertrophy in rats at high altitude. If so, we wanted to determine whether beta-receptor blockade or some other drug action were involved and whether the heart, the lung vessels, or blood alterations were affected. In rats, chronic treatment with DL-propranolol (2 mg/kg ip once daily) reduced right ventricular hypertrophy and polycythemia of chronic high altitude. D-Propranolol and metoprolol did not reduce hypoxia-induced right ventricular hypertrophy or polycythemia. In isolated lungs from low-altitude rats treated chronically with DL-propranolol or with D-propranolol the pressor response to acute hypoxia was blunted. Chronic DL-propranolol blunted the acute hypoxic pressor response and angiotensin II induced vasoconstriction in lungs from high-altitude rats. Two effects of DL-propranolol treatment were seen: 1) blockade of beta 2-adrenergic receptors, which reduced the right ventricular hypertrophy of high altitude through reduction of hematocrit; and 2) a non-beta-effect, which reduced vascular responsiveness to acute hypoxia in the isolated lung preparation.

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Congenital erythropoietin over-expression causes “anti-pulmonary hypertensive” structural and functional changes in mice, both in normoxia and hypoxia

Thrombosis and Haemostasis ◽

10.1160/th05-02-0104 ◽

2005 ◽

Vol 94 (09) ◽

pp. 630-638 ◽

Cited By ~ 25

Author(s):

Daniel Manz ◽

Daniela Buchspies ◽

Stephan Keller ◽

Tanja Mehling ◽

Robert Voswinckel ◽

...

Keyword(s):

Right Ventricular ◽

Vascular Resistance ◽

Ventricular Hypertrophy ◽

Chronic Hypoxia ◽

Acute Hypoxia ◽

Right Ventricular Hypertrophy ◽

Pulmonary Vasculature ◽

Functional Changes ◽

Over Expression ◽

Alveolar Hypoxia

SummaryAcute alveolar hypoxia causes pulmonary vasoconstriction that matches lung perfusion to ventilation to optimize gas exchange. Chronic alveolar hypoxia induces pulmonary hypertension, characterized by increased muscularization of the pulmonary vasculature and right ventricular hypertrophy. Elevated erythropoietin (EPO) plasma levels increase hematocrit and blood viscosity and may affect structure and function of the pulmonary circulation. To differentiate between the direct effects of hypoxia and those linked to a hypoxia-induced increase in EPO/hematocrit levels, we investigated the lung vasculature in transgenic mice constitutively over-expressing EPO (termed tg6) upon exposure to normoxia and chronic hypoxia. Despite increased hematocrit levels (∼0.86),tg6 mice kept in normoxia did not develop selective right ventricular hypertrophy. The portion of vessels with a diameter of 51–95 μm and >155 μm was increased whereas the portion of small vessels (30–50 μm) was decreased. Pulmonary vascular resistance and the strength of hypoxic vasoconstriction measured in isolated perfused lungs were decreased. Vasoconstrictions induced by the thromboxane mimetic U46619 tended to be reduced. After chronic hypoxia (FiO2 = 0.10, 21days), vascular resistance and vasoconstrictor responses to acute hypoxia and U46619 were reduced in tg6 mice compared to wildtype controls. Chronic hypoxia increased the degree of pulmonary vascular muscularization in wildtype but not in tg6 mice that already exhibited less muscularization in normoxia. In conclusion, congenital over-expression of EPO exerts an “anti-pulmonary hypertensive” effect, both structurally and functionally, particularly obvious upon chronic hypoxia.

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