Cheyne-Stokes respiration: hypoxia plus a deep breath that interrupts hypoxic drive, initiating cyclic breathing.

In the 19th Century, Cheyne and Stokes independently reported cycles of respiration in patients with heart failure, beginning with apnea, followed by a few breaths. However Cheyne-Stokes respiration (C-SR) can also occur in healthy individuals with sleep, and was demonstrated in 1908 with voluntary hyperventilation, followed by apnea that Haldane blamed on hypoxia, subsequently called post-hyperventilation apnea. Additional theories explaining C-SR did not appear until 1954, based on control theory, specifically a feed-back regulator controlling CO(2). This certainly describes control of normal respiration, but to produce an unstable state such as C-SR requires either a very long transit time (3½ min) or an increase of the controller gain (13 times), physiologically improbable. There is general agreement that apnea initiates C-SR but that has not been well explained except for post-hyperventilation apnea, and that explanation is not compatible with a study by Nielsen and Smith in 1951. They plotted the effects of diminished oxygen on ventilation (V) in relation to CO(2) (Fig. 1). They found that the slope of V/CO(2) (gain) increased with hypoxia, but it flattened at a moderate CO(2) level and had nointercept with zero (apnea). It is also incompatible with our published findings in 1975 that showed that apnea did not occur until an extreme level of hypoxia occurred (the PO(2) fell below 10 mmHg), followed shortly by gasping. Much milder hypoxia underlies most cases of C-SR, when hypoxic drive replaces the normal CO(2)-based respiratory drive, in a failsafe role. I hypothesize that the cause of apnea is a brief interruption of hypoxic drive caused by a pulse of oxygen from a stronger than average breath, such as a sigh. The rapidity of onset of apnea in response to a pulse of oxygen, reflects the large pressure gradient for oxygen from air to lung with each breath, in contrast to CO(2). With apnea, there is a gradual fall in oxygen, resulting in a resumption of hypoxic drive, and the cycle of C-SR continues until the next large breath. This novel theory, that a pulse of oxygen interrupts hypoxic drive to cause the initiating apnea of C-SR, is compatible with the known causes of C-SR: onset of sleep, mild hypoxia with congestive heart failure, and neurologic disorders. It is also compatible with factors known to abolish C-SR: waking, oxygen supplementation, and drugs that increase alertness such as caffeine. Testing of the hypothesis would require beat by beat recording of respiration, and arterial oxygen with a response time fast enough to demonstrate the rapid suppression of hypoxic drive. Alternatively, using a different theoretical approach such as limit-cycle oscillators instead of control theory.

Innocent murmurs: a suspect diagnosis in non-pregnant adults.

The physics of turbulence include Reynolds numbers, but they argued that these do not apply for biomedical applications. However, the 2 key variables, viscosity and flow velocity, are conceptually useful. They also warned that turbulence and murmurs are not equivalent, obvious from Doppler studies of children with innocent murmurs who demonstrate no turbulence or abnormal velocities. The musical Still's murmur contrasts with the noise generated by abnormalities of heart valves. McKusick compared the Still's murmur with the Aeolian harp's strings set into vibration by the wind. He looked for analogues in the heart and suggested false chords, but he failed to acknowledge that these become flaccid during systole. McKusick did not suggest the normal chords of the septal leaflet of the tricuspid valve that are tightened in systole by papillary muscles and traverse the pulmonary outflow, nor has anyone else, to the author's knowledge. The location of the Still's murmur was found in the pulmonary outflow by microphonic catheterization. The innocent ejection murmurs in children and pregnant women are not musical but are associated with decreased hematocrit and increased ejection velocity compared to nonpregnant adults. The aorta has been suggested as the origin of Still's murmur, but that study was done in older adults with angina who presumably had aortic valvular sclerosis. In conclusion, innocent murmurs in childhood are not normally found in adults, except for pregnant women whose blood viscosity and velocity resemble children's. When murmurs are found in nonpregnant adults, echocardiography is prudent.

A critical review of the American College of Cardiology/American Heart Association practice guidelines on bicuspid aortic valve with dilated ascending aorta.

The 2006 practice guidelines from the American College of Cardiology and the American Heart Association recommend prophylactic aortic replacement for even an asymptomatic patient with a bicuspid aortic valve (BAV) when the aortic dimensions exceed arbitrary ranges based on Marfan syndrome, without comparing risk estimates of aortic dissection with operative risks. In the International Registry of Acute Aortic Dissection, which includes >1,000 autopsied subjects, the average age is 63 years; BAVs are found in only 3%, compared with histories of hypertension in 72%. The risk for valve-sparing aortic replacement is 4% and that for late mortality is 10%, on the basis of 5 publications. The aortic dimensions are from guidelines for Marfan syndrome, with a proved genetic weakness of connective tissue, whereas no culprit genes have been demonstrated in BAV. Although cystic medial necrosis is seen in dilated aortas associated with Marfan syndrome and BAV, it is also seen in dilated aortas with other causes. There is no convincing proof that cystic medial necrosis causes dissection or is simply an effect of dilatation. BAV is not associated with dilatation of the pulmonary arteries, in contrast to Marfan syndrome. Hemodynamic explanations for dilatation of the ascending aorta have been largely ignored because of a belief that it requires severe aortic stenosis or regurgitation. In conclusion, vascular dilatation without a genetic weakness is caused by coarse periodic vibrations from even trivial valve disorders, demonstrated experimentally. There is a natural history of progressive deterioration of the BAV, including the valve left in a valve-sparing aortic replacement, that makes the operation ill advised, as opposed to valve replacement with aortic reinforcement.

Cardiac function before and after surgery for pectus excavatum.

A 2006 meta-analysis concluded that thoracic surgery for pectus excavatum (PE) significantly improves cardiovascular function. However, that analysis was flawed by a high level of heterogeneity in the outcomes and inappropriate methods in 5 of the 8 publications analyzed. Therefore, a search of the published research from 1965 to the present was conducted, and only 5 publications were found that reported studies of cardiac function before and after operation, including 118 patients and 82 unoperated controls. Cardiac function was studied most frequently by echocardiography, despite the limitations imposed by the abnormal anatomy of pectus excavatum, but only studies that did not report cardiac or left ventricular dimensions or output were excluded. Studies using indirect estimates on the basis of oxygen pulse, which depends on several other variables, were not included. No improvements were found in left ventricular size, stroke volume, and cardiac output after surgery in 4 of 5 studies, using radionuclides, 2-dimensional echocardiography, radiographic planimetry, and cardiac output by the Fick method. Only a single study, with volumes calculated by squaring the diameter of the left ventricle from M-mode echocardiography, reported an increase (22%) in left ventricular stroke volume after operation, but that increased (17%) in the investigators' unoperated controls. This and 2 other studies used in this meta-analysis were also included in a meta-analysis conducted by Malek et al. In a fourth study, Malek et al included only the first study that found an improvement, but the final study reported no improvement. In conclusion, there is no reliable documentation of improved cardiac function from thoracic surgery for pectus excavatum.