Ventilation inhibits sympathetic action potential recruitment even during severe chemoreflex stress.

This study investigated the influence of ventilation on sympathetic action potential (AP) discharge patterns during varying levels of high chemoreflex stress. In seven trained breath-hold divers (age 33 ± 12 yr), we measured muscle sympathetic nerve activity (MSNA) at baseline, during preparatory rebreathing (RBR), and during 1) functional residual capacity apnea (FRCApnea) and 2) continued RBR. Data from RBR were analyzed at matched (i.e., to FRCApnea) hemoglobin saturation (HbSat) levels (RBRMatched) or more severe levels (RBREnd). A third protocol compared alternating periods (30 s) of FRC and RBR (FRC-RBRALT). Subjects continued each protocol until 85% volitional tolerance. AP patterns in MSNA (i.e., providing the true neural content of each sympathetic burst) were studied using wavelet-based methodology. First, for similar levels of chemoreflex stress (both HbSat: 71 ± 6%; P = NS), RBRMatched was associated with reduced AP frequency and APs per burst compared with FRCApnea (both P < 0.001). When APs were binned according to peak-to-peak amplitude (i.e., into clusters), total AP clusters increased during FRCApnea (+10 ± 2; P < 0.001) but not during RBRMatched (+1 ± 2; P = NS). Second, despite more severe chemoreflex stress during RBREnd (HbSat: 56 ± 13 vs. 71 ± 6%; P < 0.001), RBREnd was associated with a restrained increase in the APs per burst (FRCApnea: +18 ± 7; RBREnd: +11 ± 5) and total AP clusters (FRCApnea: +10 ± 2; RBREnd: +6 ± 4) (both P < 0.01). During FRC-RBRALT, all periods of FRC elicited sympathetic AP recruitment (all P < 0.001), whereas all periods of RBR were associated with complete withdrawal of AP recruitment (all P = NS). Presently, we demonstrate that ventilation per se restrains and/or inhibits sympathetic axonal recruitment during high, and even extreme, chemoreflex stress.NEW & NOTEWORTHY The current study demonstrates that the sympathetic neural recruitment patterns observed during chemoreflex activation induced by rebreathing or apnea are restrained and/or inhibited by the act of ventilation per se, despite similar, or even greater, levels of severe chemoreflex stress. Therefore, ventilation modulates not only the timing of sympathetic bursts but also the within-burst axonal recruitment normally observed during progressive chemoreflex stress.

Resting arterial hypoxaemia in subjects with chronic heart failure, pulmonary hypertension and patent foramen ovale.

NEW FINDINGS: What is the central question of this study? Does a patent foramen ovale contribute to resting arterial hypoxaemia, defined as arterial oxygen saturation <95%, in subjects with chronic heart failure with or without pulmonary arterial hypertension? What is the main finding and its importance? The presence of a patent foramen ovale contributed to resting arterial hypoxaemia only in subjects with chronic heart failure with pulmonary arterial hypertension. These data suggest that the presence of a patent foramen ovale should be considered in chronic heart failure patients with arterial hypoxaemia and pulmonary hypertension. The roles of intrapulmonary and intracardiac shunt in contributing to arterial hypoxaemia at rest in subjects with chronic heart failure (CHF) have not been well investigated. We hypothesized that blood flow through intrapulmonary arteriovenous anastomoses (Q̇ IPAVA ) and/or patent foramen ovale (Q̇ PFO ) could potentially contribute to arterial hypoxaemia and, with pulmonary hypertension (PH) secondary to CHF, this contribution may be exacerbated. Fifty-six subjects with CHF (New York Heart Association Classes I-III), with (+) or without (-) PH [defined as peak tricuspid regurgitation velocity ≥2.9 m s(-1) (CHF PH+, n = 32) and peak tricuspid regurgitation velocity ≤2.8 m s(-1) (CHF PH-, n = 24)], underwent arterial blood gas analysis and transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect Q̇ IPAVA and Q̇ PFO . Seventeen of 56 subjects with CHF (30%) had Q̇ PFO , but only four of 56 subjects with CHF had Q̇ IPAVA (7%), both similar to age- and sex-matched control subjects. Mean arterial oxygen saturation (SaO2) was lower in subjects with Q̇ PFO . Only CHF PH+ subjects with Q̇ PFO had arterial hypoxaemia (mean SaO2 <95%). Bubble scores assessed using transthoracic saline contrast echocardiography were correlated with microembolic signals detected with transcranial Doppler in subjects with Q̇ PFO . Significant Q̇ IPAVA was not present in either CHF PH+ or PH- subjects, suggesting that Q̇ IPAVA is not dependent on increased pulmonary pressure and does not contribute significantly to arterial hypoxaemia in older subjects with CHF. Given that SaO2 was lower in all subjects with CHF who had Q̇ PFO compared with those without Q̇ PFO , a patent foramen ovale should be considered when determining potential causes of arterial hypoxaemia, because Q̇ PFO was present in 30% of these subjects.

Dynamic diaphragmatic MRI during apnea struggle phase in breath-hold divers.

The purpose of the study was to provide insight in diaphragmatic involuntary breathing movements (IBM) during struggle phase of apnea at total lung capacity (TLC) and functional residual capacity (FRC) using magnetic resonance imaging along with measurements of hemodynamics and arterial oxygenation. The study was performed in eight elite breath-hold divers. There was a similar increase in diaphragmatic cranio-caudal excursions towards the end of TLC and FRC apnea. The greatest diaphragmatic excursion in both apneas and during tidal breathing was in the middle and posterior part of the diaphragm. Diaphragm thickness in elite BHD was within the reference range of normal values suggesting no diaphragmatic hypertrophy in this population. We found that the range of diaphragmatic excursions increases toward the end of apneas. Additionally, our data suggest that the diaphragm participates in IBM occurrence and that various segments of the diaphragm behave nonhomogenously both in tidal breathing and IBMs.

The effects of nitroglycerin, norepinephrine and aminophylline on intrapulmonary arteriovenous anastomoses in healthy humans at rest.

We have investigated the effects of the intravenous infusion of nitroglycerin (NTG), norepinephrine (NE) and aminophylline (AMP) on the opening and recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) in healthy humans at rest. In ten volunteers saline contrast echocardiography was performed during administration of two doses of the NTG (3µgkg(-1)min(-1) and 6µgkg(-1)min(-1)) and NE (0.1µgkg(-1)min(-1) and 0.25µgkg(-1)min(-1)) as well as 30min following the administration of AMP at rate of 6mgkg(-1). Echocardiography was used to assign bubble scores (0-5) based on the number and spatial distribution of bubbles in the left ventricle. Doppler ultrasound was used to estimate pulmonary artery systolic pressure. Using a Finometer the following hemodynamic parameters were assessed: heart rate, stroke volume, cardiac output, total peripheral resistance as well as systolic, diastolic and mean arterial pressure. The most important finding from the current study was that nitroglycerin, norepinephrine and aminophylline in the applied doses were not found to promote IPAVA opening in healthy humans at rest.

The Effects of Involuntary Respiratory Contractions on Cerebral Blood Flow during Maximal Apnoea in Trained Divers.

The effects of involuntary respiratory contractions on the cerebral blood flow response to maximal apnoea is presently unclear. We hypothesised that while respiratory contractions may augment left ventricular stroke volume, cardiac output and ultimately cerebral blood flow during the struggle phase, these contractions would simultaneously cause marked 'respiratory' variability in blood flow to the brain. Respiratory, cardiovascular and cerebrovascular parameters were measured in ten trained, male apnoea divers during maximal 'dry' breath holding. Intrathoracic pressure was estimated via oesophageal pressure. Left ventricular stroke volume, cardiac output and mean arterial pressure were monitored using finger photoplethysmography, and cerebral blood flow velocity was obtained using transcranial ultrasound. The increasingly negative inspiratory intrathoracic pressure swings of the struggle phase significantly influenced the rise in left ventricular stroke volume (R (2) = 0.63, P<0.05), thereby contributing to the increase in cerebral blood flow velocity throughout this phase of apnoea. However, these contractions also caused marked respiratory variability in left ventricular stroke volume, cardiac output, mean arterial pressure and cerebral blood flow velocity during the struggle phase (R (2) = 0.99, P<0.05). Interestingly, the magnitude of respiratory variability in cerebral blood flow velocity was inversely correlated with struggle phase duration (R (2) = 0.71, P<0.05). This study confirms the hypothesis that, on the one hand, involuntary respiratory contractions facilitate cerebral haemodynamics during the struggle phase while, on the other, these contractions produce marked respiratory variability in blood flow to the brain. In addition, our findings indicate that such variability in cerebral blood flow negatively impacts on struggle phase duration, and thus impairs breath holding performance.

The influence of varying inspired fractions of O2 and CO2 on the development of involuntary breathing movements during maximal apnoea.

The growing urge to breathe that occurs during breath-holding results in development of involuntary breathing movements (IBMs). The present study determined whether IBMs are initiated at critical levels of hypercapnia and/or hypoxia during maximal apnoea. Arterial blood gasses at the onset of IBM were monitored during maximal voluntary breath-holds. Eleven healthy men performed breath holds after breathing air, hyperoxic-normocapnia, hypoxic-normocapnia, and normoxic-hypercapnia. Pre-breathing of the gas mixtures facilitated the IBM onset, reducing the time-to-onset for ∼46% (hyperoxic condition) and for ∼80% (hypoxic condition) compared to the normoxic air breathing time. A strong correlation (R=0.83, P=0.002) between arterial partial pressure of CO2 (PaCO2) at IBM onset after pre-breathing hyperoxic and hypercapnic gas mixtures was observed, suggesting the existence of a possible IBM PaCO2 threshold level of ∼6.5 ± 0.5 kPa. No clear "threshold" was observed for partial pressure of arterial O2(PaO2). However, we observed that IBM onset was influenced, in part, by an interaction between PaO2 and PaCO2 levels during maximal apnoea. This study demonstrated the complex interaction between arterial blood-gases and the physiological response to maximal breath holding.

Determinants of arterial gas embolism after scuba diving.

Scuba diving is associated with breathing gas at increased pressure, which often leads to tissue gas supersaturation during ascent and the formation of venous gas emboli (VGE). VGE crossover to systemic arteries (arterialization), mostly through the patent foramen ovale, has been implicated in various diving-related pathologies. Since recent research has shown that arterializations frequently occur in the absence of cardiac septal defects, our aim was to investigate the mechanisms responsible for these events. Divers who tested negative for patent foramen ovale were subjected to laboratory testing where agitated saline contrast bubbles were injected in the cubital vein at rest and exercise. The individual propensity for transpulmonary bubble passage was evaluated echocardiographically. The same subjects performed a standard air dive followed by an echosonographic assessment of VGE generation (graded on a scale of 0-5) and distribution. Twenty-three of thirty-four subjects allowed the transpulmonary passage of saline contrast bubbles in the laboratory at rest or after a mild/moderate exercise, and nine of them arterialized after a field dive. All subjects with postdive arterialization had bubble loads reaching or exceeding grade 4B in the right heart. In individuals without transpulmonary passage of saline contrast bubbles, injected either at rest or after an exercise bout, no postdive arterialization was detected. Therefore, postdive VGE arterialization occurs in subjects that meet two criteria: 1) transpulmonary shunting of contrast bubbles at rest or at mild/moderate exercise and 2) VGE generation after a dive reaches the threshold grade. These findings may represent a novel concept in approach to diving, where diving routines will be tailored individually.

Combined usage of inhaled and intravenous milrinone in pulmonary hypertension after heart valve surgery.

Secondary pulmonary hypertension is a frequent condition after heart valve surgery. It may significantly complicate the perioperative management and increase patients' morbidity and mortality. The treatment has not been yet completely defined principally because of lack of the selectivity of drugs for the pulmonary vasculature. The usage of inhaled milrinone could be the possible therapeutic option. Inodilator milrinone is commonly used intravenously for patients with pulmonary hypertension and ventricular dysfunction in cardiac surgery. The decrease in systemic vascular resistance frequently necessitates concomitant use of norepinephrine. Pulmonary vasodilators might be more effective and also devoid of potentially dangerous systemic side effects if applied by inhalation, thus acting predominantly on pulmonary circulation. There are only few reports of inhaled milrinone usage in adult post cardiac surgical patients. We reported 2 patients with severe pulmonary hypertension after valve surgery. Because of desperate clinical situation, we decided to use the combination of inhaled and intravenous milrinone. Inhaled milrinone was delivered by means of pneumatic medication nebulizer dissolved with saline in final concentration of 0.5 mg/ml. The nebulizer was attached to the inspiratory limb of the ventilator circuit, just before the Y-piece. We obtained satisfactory reduction in mean pulmonary artery pressure in both patients, and they were successfully extubated and discharged. Although it is a very small sample of patients, we conclude that the combination of inhaled and intravenous milrinone could be an effective treatment of secondary pulmonary hypertension in high-risk cardiac valve surgery patient. The exact indications for inhaled milrinone usage, optimal concentrations for this route, and the beginning and duration of treatment are yet to be determined.

Spleen and cardiovascular function during short apneas in divers.

We investigated the spleen volume changes as related to the cardiovascular responses during short-duration apneas at rest. We used dynamic ultrasound splenic imaging and noninvasive photoplethysmographic cardiovascular measurements before, during, and after 15-20 s apneas in seven trained divers. The role of baroreflex was studied by intravenous bolus of vasodilating drug trinitrosan during tidal breathing. The role of lung volume was studied by comparing the apneas at near-maximal lung volume with apneas after inhaling tidal volume, with and without cold forehead stimulation. In apneas at near maximal lung volume, a 20% reduction in splenic volume (P = 0.03) was observed as early as 3 s after the onset of breath holding. Around that time the heart rate increased, the mean arterial pressure abruptly decreased from 89.6 to 66.7 mmHg (P = 0.02), and cardiac output decreased, on account of reduction in stroke volume. Intravenous application of trinitrosan resulted in approximately 6-mmHg decrement in mean arterial pressure, while the splenic volume decreased for approximately 13%. In apneas at low lung volume, the early splenic contraction was also observed, 10% without and 12% with cold forehead stimulation, although the mean arterial pressure did not change or even increased, respectively. In conclusion, the spleen contraction is present at the beginning of apnea, accentuated by cold forehead stimulation. At large, but not small, lung volume, this initial contraction is probably facilitated by downloaded baroreflex in conditions of decreased blood pressure and cardiac output.

Comparison of on-demand vs planned relaparotomy for treatment of severe intra-abdominal infections.

AIM: To compare morbidity and mortality of patients with severe intra-abdominal infections after two types of surgical treatment, on-demand ("wait and see") relaparotomy and modified planned relaparotomy. METHODS: We prospectively analyzed the outcomes of 65 patients with severe peritonitis surgically treated in two Croatian hospitals. In one hospital, 34 patients were treated on-demand, and in another hospital 31 patients were treated by planned relaparotomy. We compared severe postoperative complications, mortality, and length of hospital stay in the two groups of patients. RESULTS: Severity of patient's disease, as measured from preoperative group-average Acute Physiology and Chronic Health Evaluation (APACHE) II scores, was comparable in both on-demand and planned relaparotomy groups. The mortality rate was higher in patients operated on-demand (59% vs 29%, P=0.024). In nonadjusted model, the relative risk of dying was 2.5-fold higher for patients treated by on-demand operation in comparison with planned relaparatomy (P=0.030). However, after the adjustment of the survival data for individual patient's sex and APACHE II scores, the difference in the relative risk became non-significant (P=0.178). The patients who died had higher APACHE II scores (26.1+/-8.9 vs 19.7+/-5.9, P=0.009). Relative risk of dying per 5-point increase in APACHE II score was 1.24 (95% confidence interval, 1.01-1.51; P=0.039), irrespective of the surgical technique. CONCLUSIONS: Patients with severe peritonitis treated with planned relaparotomy seemed to have lower mortality. However, the relative risk of dying was not statistically different between the on-demand and planned relaparotomy groups after adjustment for preoperative APACHE II scores. The severity of disease rather than surgical approach plays more important role in survival of these patients.