Gunnar Nicolaysen

Inspiratory impedance threshold valve during CPR

The use of an inspiratory impedance threshold valve (ITV) during cardiopulmonary resuscitation (CPR) should reduce intrathoracic pressure during natural chest recoil or active chest decompression. This might in turn improve venous return and thereby organ blood flow. The haemodynamic effects during both standard CPR and active compression-decompression (ACD)-CPR with and without the ITV, therefore, were studied in a well-established porcine model with cross-over design. Sixteen pigs were randomised to one of four methods initially, changing the method every fifth minute during mechanical chest compression at 100 min(-1). Myocardial blood flow was doubled when the valve was added to standard CPR, median (q25-q75) 14 (3-47) versus 27 (9-51) ml min(-1) 100 g(-1) (P=0.001). ACD-CPR caused a similar increase, while adding the ITV to ACD-CPR only tended to increase myocardial blood flow (P=0.077). Varying the technique had no effect on cerebral, kidney or carotid blood flow, coronary perfusion pressure, expired CO(2) concentrations or blood gases. The valve is a promising new tool in CPR, but more independent studies of the device are needed.

Effects of various degrees of compression and active decompression on haemodynamics, end-tidal CO2, and ventilation during cardiopulmonary resuscitation of pigs

UNLABELLED The effects of various degrees of compression and active decompression during cardiopulmonary resuscitation were tested in a randomized cross-over-design during ventricular fibrillation in eight pigs using an automatic hydraulic chest compression device. Compared with 4/0 (compression/decompression in cm), mean carotid arterial blood flow rose by 60% with 5/0, by 90% with 4/2 and 4/3, and 105% with 5/2. Two cm active decompression increased mean brain and myocardial blood flow by 53% and 37%, respectively, as compared with 4/0. Increasing standard compression from 4 to 5 cm caused no further increase in brain or heart tissue blood flow whether or not combined with active decompression. Tissue blood flow remained unchanged or decreased when active decompression (4/3) caused that 50% of the pigs were lifted from the table due to the force required. Myocardial blood flow was reduced with 5/0 vs. 4/0 despite no reduction in end decompression coronary perfusion pressure ((aortic-right atrial pressure) (CPP), (7 +/- 8 mmHg with 4/0, 14 +/- 11 mmHg with 5/0)(NS)). End decompression CPP increased by 186% with 4/2 vs. 4/0, by 200% with 4/3, and by 300% with 5/2. Endo-tracheal partial pressure of CO2 was significantly increased during the compression phase of active decompression CPR compared with standard CPR. Active decompression CPR generated an significantly increased ventilation compared with standard CPR. CONCLUSION Carotid and tissue blood flow, ventilation, and CPP increase with 2 cm of active decompression. An attempt to further increase the level of active decompression or increasing the compression depth from 4 to 5 cm did not improve organ blood flow.

Positive end-expiratory pressure affects regional redistribution of ventilation differently in prone and supine sheep

Objective:To examine interactions between positive end-expiratory pressure (PEEP) and posture on regional distribution of ventilation and to compare measurements of regional ventilation with two aerosols: a wet fluorescent microsphere aerosol (FMS, median mass aerodynamic diameter 1.1 &mgr;m) and a dry 99mTc-labeled carbon particle aerosol (Technegas, TG, median mass aerodynamic diameter ≈0.1 &mgr;m). Design:Experimental study. Setting:Academic laboratory. Subjects:Anesthetized and mechanically ventilated sheep (n = 16). Interventions:Four conditions were studied: prone or supine posture with or without 10 cm H2O PEEP. Measurements and Main results:Comparisons of FMS and TG were made in five animals. The median correlation coefficient of the two ventilation tracers was .95 (range, .91–.96). The mean ventilation per unit weight of dry lung for horizontal planes was almost identical whether measured with TG or FMS. The distribution of ventilation was assessed by analyzing deposition of aerosol in about 1,000 lung regions per animal. Distribution of ventilation down the vertical axis was linear in prone (the slope indicated a dorsal-to-ventral three-fold difference in ventilation) but unimodal in supine animals with the mode in the center of the lung. Redistribution of ventilation with 10 PEEP differed between posture, shifting the mode in supine toward dependent lung regions while eliminating the dorsal-to-ventral gradient in prone. The regional heterogeneity in ventilation was greater in supine sheep at both levels of PEEP, and this was due mostly to greater isogravitational heterogeneity in supine than in prone position. Conclusions:The wet fluorescent microsphere aerosol was as reliable as Technegas for high-resolution measurements of regional ventilation. The markedly different effects of 10 PEEP in supine and prone sheep may have important implications for gas exchange both in noninjured and injured lungs.

Effect of different compression-decompression cycles on haemodynamics during ACD-CPR in pigs

The haemodynamic effects of variations in the relative duration of the compression and active decompression (4 cm/2 cm) during active compression-decompression cardiopulmonary resuscitation (ACD-CPR), 30/70, 50/50 and 70/30, were tested in a randomized cross-over design during ventricular fibrillation in seven anaesthetized pigs (17-23 kg) using an automatic hydraulic chest compression-decompression device. Duty cycles of 50/50 and 70/30 gave significantly higher values than 30/70 for mean carotid blood flow (32 and 36 vs. 21 ml min-1, transit time flow probe, cerebral blood flow (30 and 34 vs. 19, radionuclide microspheres), mean aortic pressure (35 and 41 vs. 29 mmHg) and mean right atrial pressure (24 and 33 vs. 16 mmHg). A higher mean aortic, mean right atrial and mean left ventricular pressure for 70/30 were the only significant differences between 50/50 and 70/30. There were no differences in myocardial blood flow (radionuclide microspheres) or coronary perfusion pressure (CPP, aortic-right atrial pressure) between the three different duty cycles. CPP was positive in both the early and late compression period and during the whole decompression period. The expired CO2 was significantly higher with 70/30 than 30/70 during the compression phase of ACD-CPR. Beyond that no significant differences in the expired CO2 levels were observed. In conclusion a reduction of the compression period to 30% during ACD-CPR reduced the cerebral circulation, the mean aortic and right atrial pressures with no effect on the myocardial blood flow of varying the compression-decompression cycle.

Improved haemodynamics with increased compression-decompression rates during ACD-CPR in pigs

The haemodynamic effects of variations in the compression-decompression frequency, 60, 90 and 120 min(-1) during ACD-CPR, were tested in a randomized cross-over design during ventricular fibrillation (VF) in 12 anaesthetized pigs (17-22 kg) using an automatic hydraulic chest compression-decompression device. There were significant increases with increasing frequency for mean (+/- S.D.) carotid blood flow (17 +/- 5, 25 +/- 9 and 36 +/- 12 ml min(-1), transit time flow probe), cerebral blood flow (17 +/- 7, 30 +/- 17 and 40 +/- 13 ml min(-1) 100 g(-1), radionuclide microspheres) and mean aortic pressure (34 +/- 8, 37 +/- 10 and 43 +/- 7 mmHg), respectively. Myocardial blood flow (radionuclide microspheres) and diastolic coronary perfusion pressure, CPP, increased significantly from 60 to 90 min(-1) with no further significant increase to 120 min(-1) (28 +/- 13, 46 +/- 23 and 49 +/- 19 ml min(-1) 100 g(-1) and 25 +/- 8, 31 +/- 11 and 32 +/- 9 mmHg, respectively). Renal and hepatic blood flow also increased with increasing rate. No significant differences in the expired CO2 levels were observed. In conclusion increasing the compression-decompression frequency from 60 to 90 and 120 min(-1) improved the haemodynamics during ACD-CPR in a pig model with VF.

Differences and similarities between human and rabbit neutrophil granulocyte responses in vitro: the effects of zymosan‐activated plasma, phorbol myristate acetate and n‐formyl‐methionyl‐leucyl‐phenylalanine

The amount of reactive oxygen intermediates (ROI) generated by activated polymorphonuclear neutrophils (PMN), as well as the closeness of contact between PMN and vessel wall, may determine whether PMN activators will induce the adult respiratory distress syndrome. We examined the ROI‐generating and aggregating effects of zymosan activated plasma (ZAP), phorbol myristate acetate (PMA) and n‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP), on isolated human and rabbit PMN. PMA, after a short lag phase, induced a large and long‐lasting increase in ROI generation. The initial peak response was higher and more rapid in human than in rabbit cells. The reaction to FMLP occurred almost instantaneously, but was much weaker than that to PMA, and ROI generation returned to near baseline in less than 10 min. No species difference was seen. ZAP caused an FMLP‐like ROI response in human cells, whereas no response was observed in rabbit PMN. PMN aggregation was induced by all three activators, most markedly by PMA. No species difference was detected for PMA; FMLP gave a stronger aggregation of rabbit than of human PMN, however, while the opposite was true for ZAP. In conclusion, ZAP was a potent stimulus for PMN aggregation, but had modest (or no) effects on the production of ROI. Marked differences between human and rabbit PMN responses were observed.

Lymph flow pattern in the intact thoracic duct in sheep

1 To study the lymph flow dynamics in the intact thoracic duct, we applied an ultrasound transit‐time flow probe in seven anaesthetized and four unanaesthetized adult sheep (.60 kg). In unanaesthetized non‐fasting animals we found that lymph flow in the thoracic duct was always regular pulsatile (pulsation frequency, 5.2 ± 0.8 min−1) with no relation to heart or respiratory activity. At baseline the peak level of the thoracic duct pulse flow was 11.6–20.7 ml min−1 with a nadir of 0–3.6 ml min−1. Mean lymph flow was 5.4 ± 3.1 ml min−1. The flow pattern of lymph in the thoracic duct was essentially the same in the anaesthetized animals. 2 In both the anaesthetized and unanaesthetized animals, the lymph flow response to a stepwise increase in the outflow venous pressure showed interindividual variation. Some were sensitive to any increase in outflow venous pressure, but others were resistant in that lymph flow did not decrease until outflow venous pressure was increased to higher levels. This resistance was also observed in the high lymph flow condition produced by fluid infusion in the anaesthetized animal and mechanical constriction of the caudal vena cava in the unanaesthetized animals. Pulsation frequency of the thoracic duct flow initially increased and then decreased with a stepwise increase in the outflow venous pressure. This initial increase might be a compensatory response to maintain lymph flow against elevated outflow venous pressure. 3 To test the effect of long‐term outflow venous pressure elevation in unanaesthetized sheep, outflow venous pressure was increased by inflation of a cuff around the cranial vena cava for 1, 5 or 25 h. The cuff was inflated to a level where lymph flow was reduced. Lymph flow remained low or decreased further during the entire cuff‐inflation period. We calculated the lymph debt caused by the outflow venous pressure elevation and the amount ‘repaid’ when venous pressure returned to normal. Lymph debt for 25 h was 6400 ml but only 200 ml was repaid. Since we observed no visible oedema formation in the lower body of the sheep, the non‐colloidal components of the lymph must have been reabsorbed into the bloodstream, most likely in the lymph nodes.

Decreased blood flow to rat bone marrow, bone, spleen, and liver in acute leukemia

An acute promyelocytic leukemia in the rat (BNML) has been used in model studies on pathogenesis and therapy of human acute myeloid leukemia. The blood supply to bone marrow during BNML development has hitherto not been examined, even though in general, blood flow to hematopoietic tissues might affect drug treatment and marrow transplantation regimes. We measured the perfusion of various organs during the course of the disease in untreated rats and in rats given one injection of cyclophosphamide treatment. Organ perfusion was measured with radioactive microspheres. Blood flow per gram tissue to the bone marrow, bone, spleen, and liver declined gradually during the leukemic progression, thus paralleling the growth of leukemic deposits. Cyclophosphamide treatment retarded, but did not reverse, the decreasing perfusion of these tissues.

G‐CSF enhances the proliferation and mobilization, but not the maturation rate, of murine myeloid cells

Objectives:  Whether G‐CSF enhances the maturation of neutrophilic granulocytes or just accelerates the mobilization of mature and maturing granulocytes from bone marrow to blood, or both, is not clear. Using an in vivo culture system where such mobilization cannot take place, we previously showed that G‐CSF did not accelerate maturation. To further clarify the role of G‐CSF, we now have examined its effect on murine granulopoiesis in situ.

Uneven perfusion within single cat muscles: Nitric oxide and citrate synthase play no role

There is an unexplained, marked regional heterogeneity in perfusion within single skeletal muscles both in dogs and rabbits. We asked if a similar distribution of perfusion was present within cat muscles. If present, we wanted to assess the possible roles of nitric oxide (NO) mediated vasodilation and citrate synthase (CS) activity for the regulation of this perfusion pattern. Perfusion was determined in 0.25 g regions within the gastrocnemius muscles by trapping of microspheres. We studied awake or anesthetized cats before and during inhibition of NO-formation using N-monomethyl-L-arginine. The CS activity was determined in homogenates of these regions. The coefficient of variation corrected for the Poisson distribution of microspheres (CVc) for the regional perfusion averaged 0.39. Despite a 25% reduction in perfusion to the whole muscles as compared to control, the uneven distribution of perfusion was not affected by blocking NO formation. Regional perfusion was not correlated to regional CS activity. Even if the regional distribution of CS activity also showed a scatter, mean coefficient of variation corrected for methodological error = 0.20, it was markedly less than that for perfusion. We conclude that neither NO vasodilation nor CS activity play an important role in the regulation of the regional perfusion pattern within single cat muscles.