662 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



In circulator\' models or acute animal experiments 

 even a slight diastolic regurgitation into the left 

 ventricle reduces its effectixe output. In man, how- 

 ever, both effective stroke output and cardiac output 

 may be maintained within normal limits. Ex'en with 

 more pronounced leaks and a decrease in stroke out- 

 put the cardiac output ma\' be kept normal through an 

 increase in heart rate which ser\es to decrease the 

 diastolic time during the cardiac cycle. Tachycardia 

 is, therefore, beneficial in clinical cases of aortic 

 regurgitation. The regurgitation of blood from the 

 aorta in early diastole in aortic insufficiency may 

 actually constitute 35 to 60 per cent of the stroke 

 volume. In man no reliable method of determining 

 the regurgitated amount exists, although attempts 

 have been made to estimate total and effective 

 stroke output through a combination of different 

 methods, leading to estimates of from 15 to 50 per 

 cent regurgitated portion of total stroke volume. In 

 another estimate made by Braunwald ?/ al. (28), using 

 a dye dilution method with the injection of dye in 

 the aorta, the regurgitant volume was estimated to 

 vary between 27 and 73 per cent of the cardiac output 

 corresponding to total aortic regurgitant flows rang- 

 ing from 1.8 to 5.6 liters per min. 



Both animal and human studies thus indicate that a 

 normal effective cardiac output can be maintained 

 through the increase of end-diastolic tension, oc- 

 curring as a result of the increased ventricular filling 

 from the aorta. The regurgitated \olume ma\- be 

 equal to, or larger than, the net output. Most of it is 

 regurgitated early and before any filling of the 

 ventricle from the left atrium occurs. The size of the 

 regurgitated \olumc is to a great extent determined 

 by the actual area of the aortic orifice, and only to a 

 small extent by the heart rate or peripheral resistance, 

 as long as the myocardium responds normalK . When 

 the myocardium starts failing, the mitral ring dilates 

 with the ventricle. With mitral incompetence added 

 to the left ventricular failiu'e the left atrial and pul- 

 monary venous pressure increase rapidh, causing 

 pulmonary edema or chronic pulmonary congestion. 

 Once this train of events has started there is little 

 chance for the left ventricular myocardium to regain 

 its abilitN' to contract normalU'. This explains the 

 common clinical experience of the rapidlv fatal 

 course of aortic incompetence once signs of failure 

 have appeared. 



Mitral Stenosis 



The study of experimental mitral stenosis has been 

 especialh' ditiicult, since the production of this lesit)n 



in the laboratory animal has frequentlv been accom- 

 panied by secondary changes. These have usually 

 been caused by artifacts in the form of inadvertent 

 alterations in coronary circulation, the simultaneous 

 production of aortic stenosis, or even constriction 

 of the great veins. Such mishaps have certainly 

 caused much of the disagreement between the results 

 achie\cd by the earlier workers in this field. 



Katz & Spiegel (iii) were aware of these diffi- 

 culties when they produced mitral stenosis in dogs, 

 using ligatures placed around the mitral orifice and 

 tightened. They studied the acute effects of producing 

 stenosis on tlie pressure pulses in the left atrium, left 

 \entricle, aorta, pulmonary artery, and right ven- 

 tricle; but they did not measure blood ffow. 



The general pressure level of the left atrium was 

 raised with a marked increase in magnitude of the 

 left atrial contraction when stenosis was produced. 

 The initial end-diastolic pressure of the left \entricle 

 showed variable changes (perhaps due to artifacts), 

 whereas the maximum left ventricular pressure 

 decreased. The systolic, diastolic, and pulse pressure 

 in the aorta fell. The heart rate usualK', but not 

 always, slowed. This caused a marked abbre\iation 

 of the ejection and total systolic time in both \en- 

 tricles. The right ventricular response to the produc- 

 tion of mitral stenosis was \ariable, the pressures 

 sometimes fell, sometimes rose, or remained im- 

 changed. These \arying results were thought to be 

 due only partly to stenosis, causing impediment of 

 flow to the left ventricle and damming back of fluid 

 in the pulmonary circuit. In part, they depended on 

 the decrease in coronary flow resulting from the fall 

 in the arterial blood pressure. 



In two fairlv recent publications on the effect of 

 experimentally created mitral stenosis in dogs the 

 results are also partly conflicting. Ev'en though it 

 was possible in both studies to keep the dogs alive for 

 a considerable time with the mitral lesion, the results 

 differed markedly in regard to the effect on the 

 pulmonary arterial pressure and the right heart. 



One of the groups making the study found that the 

 elesation of the pulmonary venous pressure was 

 associated with a decrease in the pressure gradient 

 from the pulmonary artery to the pulmonary veins, 

 with no change in cardiac output, and thus a decrease 

 in pulmonary va.scular resistance. These findings were 

 similar to those found in isolated lungs when the 

 venous pressure was passi\'ely ele\'ated (25, 95). The 

 other group found that the experimental mitral 

 stenosis always resulted in right ventricular hyper- 

 tension, similar to that found in patients with mitral 

 stenosis (132). The [Pulmonary arterial pressure 



