Cardiovascular responses to hypoxia

In late gestation, the fetal cardiovascular response to hypoxia is typified by a rapid, transient bradycardia and increased heart rate variability (21,22). The bradycardia reaches a nadir approximately 1-2 min after the onset of the hypoxic insult (15,23) and, presumably, economizes on myocardial oxygen consumption. Fetal hypoxic bradycardia occurs at the onset of hypoxic hypoxia (5), umbilical cord occlusion (24,25), and uterine artery occlusion (26)— the three most common experimental hypoxic challenges. 

Koos B, Chau A, Ogunyemi D. Adenosine mediates metabolic and cardiovascular responses to hypoxia in fetal sheep. J Physiol (Lond) 1995 488(3) 761-766. 

Fritsche R, Nilsson S. Cardiovascular responses to hypoxia in the Atlantic cod, Gadus morhua. Exp Biol 1989 48 153-160. 

Opioids depress respiration via the ji2-receptor at the level of the medulla and thereby increase PCO2. Opioids reduce respiration, an effect that is fatal in the case of overdose, by a dual action. The opioids decrease both the sensitivity of the medulla to carbon dioxide concentrations and the respiratory rate. Cardiovascular function and the response to hypoxia are not compromised. By contrast, tolerance to the respiratory depressant effects of the opioids does not appear to occur, while tolerance to the emetic effects of the opioids occurs upon repeated administration. The area postrema chemoreceptor trigger zone of the medulla mediates opioid-induced vomiting. 

Midazolam depresses both cardiovascular and respiratory function, especially in elderly patients (20). As little as 0.01 mg/kg can obtund the response to hypoxia and hypercapnia (21). The simultaneous use of opiates (such as fentanyl) commonly produces hypoxia (22). 

Piacquadio K, Brace R, Cheung C. Role of vasopressin in mediation of fetal cardiovascular responses to acute hypoxia. Am J Ohstet Gynecol 1990 163(4 Pt 1) 1294-1300. 

Green LR, Bennet L, Hanson MA. The role of nitric oxide synthesis in cardiovascular responses to acute hypoxia in the late gestation sheep fetus. J Physiol (Lond) 1996 497(Pt l) 271-277. 

Blanco CE, Dawes GS, Hanson MA, McCooke HB. The response to hypoxia of arterial chemoreceptors in fetal sheep and newborn lambs. J Physiol 1984 351 25-37. Guissani D, Spencer J, Moore P, Bennet L, Hanson M. Afferent and efferent components of the cardiovascular reflex responses to acute hypoxia in term fetal sheep. J Physiol 1993 461 431 49. 

Burleson ML, Smatresk NJ. Effects of sectioning cranial nerves IX and X on cardiovascular and ventilatory reflex responses to hypoxia and NaCN in channel catfish. J Exp Biol 1990 154 407-420. 

Two genetically distinct heme oxygenases (HOs) have been characterized HO-1 is an inducible form, whereas HO-2 is constitutive. HO-2 is abundant in selective tissues such as brain and the cardiovascular system. HO-1 is highly inducible in many tissues in response to a variety of stresses, including infection, exposure to xenobiotics, hypoxia, and proinflammatory cytokines. The recognition that heme oxygenase is expressed in many different tissues led to studies of the role of heme degradation apart from the pathway for formation and elimination of bilirubin derived from destruction of senescent erythrocytes. 

There is strong evidence that STX-induced lethality is caused by a combination of central and peripheral cardiorespiratory effects. Changes in cardiac output can be attributed to the effect of STX on fast sodium channels in contractile myocardium and Purkinje fibers. Cardiovascular shock resulting from high doses of STX is in response to a combination of vascular hypotension and reduced cardiac output, followed by a lack of venous return and finally hypoxia [131-134]. 

Bergfeld, G. R., Forrester, T. Release of ATP from human erythrocytes in response to a brief period of hypoxia and hypercapnea. Cardiovascular Research, 1992, 26,40-47. 

AVP is synthesized in the fetal hypothalamus. In addition to its role in altering gene expression (e.g., POMC), plasma AVP levels also increase in response to fetal hypoxia-ischemia (30,70,71). The release of AVP is not mediated by peripheral chemoreceptor mechanisms and therefore is unlikely to contribute to the rapid cardiovascular changes at the onset of hypoxia (see above) (30). Exogenously administered AVP produces hypertension, peripheral vasoconstriction, and bradycardia (71-73), although the contribution of hypoxia-stimulated increases in AVP to the redistribution of fetal CVO is uncertain (74,75). Endothehal VI receptors mediate an AVP vasodUatory effect, which means that the net effect of AVP on the cardiovascular system is likely to reflect an integrated picture of vasoconstriction from a number of vascular beds, modulated by endothelium-dependent vasodUatory mechanisms (76). 

Severe, acute reduetion in oxygenation, for example by complete arrest of uterine flow or complete umbiheal cord occlusion, is not associated with a decrease in eerebrovascular resistance, as is seen in more mild insults. This suggests that the ability of the fetus to adapt to hypoxia has been overwhelmed. The rate at which the fetal arterial O2 content falls may be a determinant of the response elicited whether it be a rapid onset of ECoG isoelectricity (32,120), reduced regional cerebral blood flows (17), a failure of cardiovascular adaptive responses (139), an increase in eerebral lactate production (140), or a 50% reduction in cerebral metabolic rate... 

While all cells are sensitive to hypoxia to various extents, there is a speeial subset whose physiological function is to detect changing levels of O2 in either the environment or tissues and eUeit eompensatory reactions to maintain O2 uptake. These are the 02-sensitive chemoreceptors that mediate cardiovascular and ventilatory reflex responses to acute hypoxia and also play a role in long-term physiological changes in response to chronic hypoxia. Most of what we know about O2 chemoreception comes from studies on mammals where these cells are concentrated in the aortic, carotid, and pulmonary neuroepithehal bodies. It is these cells that have been examined in the greatest detail and are the subject of the bulk of this book. This chapter will focus on the 02-sensitive chemoreceptors in animals other than mammals. 

Although most patients are asymptomatic, respiratory alkalosis may cause adverse neuromuscular, cardiovascular, and gastrointestinal effects." During periods of decreased PaC02, there is a decrease in cerebral blood flow, which may be responsible for symptoms of light-headedness, confusion, decreased intellectual functioning, syncope, and seizures. Nausea and vomiting may occur, probably as a result of cerebral hypoxia. In severe respiratory alkalosis, cardiac arrhythmias may occur, due to sensitization of the myocardium to the... 

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