Ivan Palada

A single air dive reduces arterial endothelial function in man

During and after decompression from dives, gas bubbles are regularly observed in the right ventricular outflow tract. A number of studies have documented that these bubbles can lead to endothelial dysfunction in the pulmonary artery but no data exist on the effect of diving on arterial endothelial function. The present study investigated if diving or oxygen breathing would influence endothelial arterial function in man. A total of 21 divers participated in this study. Nine healthy experienced male divers with a mean age of 31 ± 5 years were compressed in a hyperbaric chamber to 280 kPa at a rate of 100 kPa min−1 breathing air and remaining at pressure for 80 min. The ascent rate during decompression was 9 kPa min−1 with a 7 min stop at 130 kPa (US Navy procedure). Another group of five experienced male divers (31 ± 6 years) breathed 60% oxygen (corresponding to the oxygen tension of air at 280 kPa) for 80 min. Before and after exposure, endothelial function was assessed in both groups as flow‐mediated dilatation (FMD) by ultrasound in the brachial artery. The results were compared to data obtained from a group of seven healthy individuals of the same age who had never dived. The dive produced few vascular bubbles, but a significant arterial diameter increase from 4.5 ± 0.7 to 4.8 ± 0.8 mm (mean ±s.d.) and a significant reduction of FMD from 9.2 ± 6.9 to 5.0 ± 6.7% were observed as an indication of reduced endothelial function. In the group breathing oxygen, arterial diameter increased significantly from 4.4 ± 0.3 mm to 4.7 ± 0.3 mm, while FMD showed an insignificant decrease. Oxygen breathing did not decrease nitroglycerine‐induced dilatation significantly. In the normal controls the arterial diameter and FMD were 4.1 ± 0.4 mm and 7.7 ± 0.2.8%, respectively. This study shows that diving can lead to acute arterial endothelial dysfunction in man and that oxygen breathing will increase arterial diameter after return to breathing air. Further studies are needed to determine if these mechanisms are involved in tissue injury following diving.

Cardiovascular Regulation During Apnea in Elite Divers

Involuntary apnea during sleep elicits sustained arterial hypertension through sympathetic activation; however, little is known about voluntary apnea, particularly in elite athletes. Their physiological adjustments are largely unknown. We measured blood pressure, heart rate, hemoglobin oxygen saturation, muscle sympathetic nerve activity, and vascular resistance before and during maximal end-inspiratory breath holds in 20 elite divers and in 15 matched control subjects. At baseline, arterial pressure and heart rate were similar in both groups. Maximal apnea time was longer in divers (1.7±0.4 versus 3.9±1.1 minutes; P<0.0001), and it was accompanied by marked oxygen desaturation (97.6±0.7% versus 77.6±13.9%; P<0.0001). At the end of apnea, divers showed a >5-fold greater muscle sympathetic nerve activity increase (P<0.01) with a massively increased pressor response compared with control subjects (9±5 versus 32±15 mm Hg; P<0.001). Vascular resistance increased in both groups, but more so in divers (79±46% versus 140±82%; P<0.01). Heart rate did not change in either group. The rise in muscle sympathetic nerve activity correlated with oxygen desaturation (r2=0.26; P<0.01) and with the increase in mean arterial pressure (r2=0.40; P<0.0001). In elite divers, breath holds for several minutes result in an excessive chemoreflex activation of sympathetic vasoconstrictor activity. Extensive sympathetically mediated peripheral vasoconstriction may help to maintain adequate oxygen supply to vital organs under asphyxic conditions that untrained subjects are not able to tolerate voluntarily. Our results are relevant to conditions featuring periodic apnea.

The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function

Diving‐induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo‐controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non‐randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow‐mediated dilatation (FMD) and heart function with increased mean PAP. Twenty‐four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P= 0.005), while right ventricle ejection fraction (RV‐EF), left ventricle EF and endocardial fractional shortening were reduced much less (∼2–3%). At the same time RV end‐systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post‐dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre‐dive placebo, whereas for most cardiovascular parameters this occurred earlier (24–48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting longer lasting negative effects.

EFFECT OF HUMAN SPLENIC CONTRACTION ON VARIATION IN CIRCULATING BLOOD CELL COUNTS

1. The human spleen sequesters 200–250 mL densely packed red blood cells. Up to 50% of this viscous blood is actively expelled into the systemic circulation during strenuous exercise or simulated apnoea (breath‐hold) diving. The contribution of splenic contraction to changes in the circulating volume of red blood cells (RBCV), as well as the venous concentration of white blood cells (WBC) and platelets (PLT), was investigated following repeated breath‐hold apnoeas.

Cerebral and peripheral hemodynamics and oxygenation during maximal dry breath-holds

The effects of maximal apneas on cerebral and brachial blood flow and oxygenation are unknown in humans. Middle cerebral artery blood velocity (MCAV), cerebral and muscle oxygenation (Sc(O2) and Sm(O2)) and brachial blood flow (BBF) were measured during apneas in breath-hold divers (BHD) and non-divers (ND). Brain oxyhemoglobin (O(2)Hb) was maintained in both groups until the end of apnea, whereas deoxyhemoglobin increased more in BHD. Therefore, Sc(O2) decreased more in BHD due to longer apnea duration and smaller initial MCAV increase. MCAV increased significantly more in BHD versus ND at the end of apnea. Cerebral desaturation for approximately 13% occurred at the end of apnea in BHD despite increased cerebral oxygen delivery for approximately 50%. Larger reduction in muscle O(2)Hb was found in BHD, with similar peripheral vasoconstriction. These data indicate that BHD have decreased Sc(O2) at the end of breath-hold despite large increases in MCAV. This is partly due delayed initial cerebral vasodilation. This study provides further evidence for the oxygen-conserving effect in elite divers.

Red wine induced modulation of vascular function: separating the role of polyphenols, ethanol, and urates

By using red wine (RW), dealcoholized red wine (DARW), polyphenols-stripped red wine (PSRW), ethanol-water solution (ET), and water (W), the role of wine polyphenols, ethanol, and urate on vascular function was examined in humans (n=9 per beverage) and on isolated rat aortic rings (n=9). Healthy males randomly consumed each beverage in a cross-over design. Plasma ethanol, catechin, and urate concentrations were measured before and 30, 60 and 120 minutes after beverage intake. Endothelial function was assessed before and 60 minutes after beverage consumption by normalized flow-mediated dilation (FMD). RW and DARW induced similar vasodilatation in the isolated vessels whereas PSRW, ET, and W did not. All ethanol-containing beverages induced similar basal vasodilatation of brachial artery. Only intake of RW resulted in enhancement of endothelial response, despite similar plasma catechin concentration after DARW. The borderline effect of RW on FMD (P=0.0531) became significant after FMD normalization (P=0.0043) that neutralized blunting effect of ethanol-induced basal vasodilatation. Effects of PSRW and ET did not differ although plasma urate increased after PSRW and not after ET, indicating lack of urate influence on endothelial response. Acute vascular effects of RW, mediated by polyphenols, cannot be predicted by plasma catechin concentration only.

Antioxidant pretreatment and reduced arterial endothelial dysfunction after diving.

INTRODUCTION We have recently shown that a single air dive leads to acute arterial vasodilation and impairment of endothelium-dependent vasodilatation in humans. Additionally we have found that predive antioxidants at the upper recommended daily allowance partially prevented some of the negative effects of the dive. In this study we prospectively evaluated the effect of long-term antioxidants at a lower RDA dose on arterial endothelial function. METHODS Eight professional male divers performed an open sea air dive to 30 msw. Brachial artery flow-mediated dilation (FMD) was assessed before and after diving. RESULTS The first dive, without antioxidants, caused significant brachial arterial diameter increase from 3.85 +/- 0.55 to 4.04 +/- 0.5 mm and a significant reduction of FMD from 7.6 +/- 2.7 to 2.8 +/- 2.1%. The second dive, with antioxidants, showed unchanged arterial diameter and significant reduction of FMD from 8.11 +/- 2.4 to 6.8 +/- 1.4%. The FMD reduction was significantly less with antioxidants. Vascular smooth muscle function, assessed by nitroglycerine (endothelium-independent dilation), was unaffected by diving. DISCUSSION This study shows that long-term antioxidant treatment at a lower RDA dose ending 3-4 h before a dive reduces the endothelial dysfunction in divers. Since the scuba dive was of a similar depth and duration to those practiced by numerous recreational divers, this study raises the possibility of routine predive supplementation with antioxidants.

Restoration of hemodynamics in apnea struggle phase in association with involuntary breathing movements

Involuntary breathing movements (IBM) that occur in the struggle phase of maximal apneas produce waves of negative intrathoracic pressure. This could augment the venous return, increasing thereby the cardiac output and gas exchange, and release the fresh blood from venous pools of spleen and liver. To test these hypotheses we used photoplethysmography and ultrasound for assessment of hemodynamics and spleen size before, during and after maximal dry apneas at large lung volume in 7 trained divers. During the easy-going phase cardiac output was reduced about 40%, due to reduction in stroke volume and in presence of reduced inferior vena cava venous return, while the spleen contracted for about 60 ml. Towards the end of the struggle phase, in presence of intense IBM, the spleen volume further decreased for about 70 ml, while cardiac output and caval flow almost renormalized. In conclusion, IBM coincide with splenic volume reduction and restoration of hemodynamics, likely facilitating the use of the last oxygen reserves before apnea cessation.

Involuntary breathing movements improve cerebral oxygenation during apnea struggle phase in elite divers

We investigated whether the involuntary breathing movements (IBM) during the struggle phase of breath holding, together with peripheral vasoconstriction and progressive hypercapnia, have a positive effect in maintaining cerebral blood volume. The central hemodynamics, arterial oxygen saturation, brain regional oxyhemoglobin (bHbO(2)), deoxyhemoglobin, and total hemoglobin changes and IBM were monitored during maximal dry breath holds in eight elite divers. The frequency of IBM increased (by approximately 100%), and their duration decreased ( approximately 30%), toward the end of the struggle phase, whereas the amplitude was unchanged (compared with the beginning of the struggle phase). In all subjects, a consistent increase in brain regional deoxyhemoglobin and total hemoglobin was also found during struggle phase, whereas bHbO(2) changed biphasically: it initially increased until the middle of the struggle phase, with the subsequent relative decline at the end of the breath hold. Mean arterial pressure was elevated during the struggle phase, although there was no further rise in the peripheral resistance, suggesting unchanged peripheral vasoconstriction and implying the beneficial influence of the IBM on the cardiac output recovery (primarily by restoration of the stroke volume). The IBM-induced short-lasting, sudden increases in mean arterial pressure were followed by similar oscillations in bHbO(2). These results suggest that an increase in the cerebral blood volume observed during the struggle phase of dry apnea is most likely caused by the IBM at the time of the hypercapnia-induced cerebral vasodilatation and peripheral vasoconstriction.

Cerebrovascular reactivity to hypercapnia is unimpaired in breath-hold divers

Hypercapnic cerebrovascular reactivity is decreased in obstructive sleep apnoea and congestive heart disease perhaps as a result of repeated apnoeas. To test the hypothesis that repeated apnoeas blunt cerebrovascular reactivity to hypercapnia, we studied breath hold divers and determined cerebrovascular reactivity by measuring changes in middle cerebral artery velocity (MCAV, cm s−1) per mmHg change in end‐tidal partial pressure of CO2 () in response to two hyperoxic hypercapnia rebreathing manoeuvres (modified Read protocol) in elite breath‐hold divers (BHD, n= 7) and non‐divers (ND, n= 7). In addition, ventilation and central (beat‐to‐beat stroke volume measurement with Modelflow technique) haemodynamics were determined. Ventilatory responses to hypercapnia were blunted in BHD versus ND largely due to lower breathing frequency. Cerebrovascular reactivity did not differ between groups (3.7 ± 1.4 versus 3.4 ± 1.3% mmHg−1 in BHD and ND, respectively; P= 0.90) and the same was found for cerebral vascular resistance and MCAV recovery to baseline after termination of the CO2 challenge. Cardiovascular parameters were not changed significantly during rebreathing in either group, except for a small increase in mean arterial pressure for both groups. Our findings indicate that the regulation of the cerebral circulation in response to hypercapnia is intact in elite breath‐hold divers, potentially as a protective mechanism against the chronic intermittent cerebral hypoxia and/or hypercapnia that occurs during breath‐hold diving. These data also suggest that factors other than repeated apnoeas contribute to the blunting of cerebrovascular reactivity in conditions like sleep apnoea.