High survival rate of 43% in out-of-hospital cardiac arrest patients in an optimised chain of survival

Aims

Survival to hospital discharge after out-of-hospital cardiac arrest (OHCA) varies widely. This study describes short-term survival after OHCA in a region with an extensive care path and a follow-up of 1 year.

Methods

Consecutive patients ≥16 years admitted to the emergency department between April 2011 and December 2012 were included. In July 2014 a follow-up took place. Socio-demographic data, characteristics of the OHCA and interventions were described and associations with survival were determined.

Results

Two hundred forty-two patients were included (73 % male, median age 65 years). In 76 % the cardiac arrest was of cardiac origin and 52 % had a shockable rhythm. In 74 % the cardiac arrest was witnessed, 76 % received bystander cardiopulmonary resuscitation and in 39 % an automatic external defibrillator (AED) was used. Of the 168 hospitalised patients, 144 underwent therapeutic procedures. A total of 105 patients survived until hospital discharge. Younger age, cardiac arrest in public area, witnessed cardiac arrest, cardiac origin with a shockable rhythm, the use of an AED, shorter time until return of spontaneous circulation, Glasgow Coma Scale (GCS) ≥13 during transport and longer length of hospital stay were associated with survival. Of the 105 survivors 72 survived for at least 1 year after cardiac arrest and 6 patients died.

Conclusion

A survival rate of 43 % after OHCA is achievable. Witnessed cardiac arrest, cardiac cause of arrest, initial cardiac rhythm and GCS ≥13 were associated with higher survival.     

1007型THUMPER心肺复苏机在急诊心肺复苏中的临床观察

目的观察1007型THUMPER心肺复苏机（萨勃机）在急诊心肺复苏中的临床效果。方法将114例心肺骤停患者分为萨勃机组59例和徒手心肺复苏组55例,两组患者均使用电除颤和药物治疗,比较两种方法在心肺复苏中的有效率。结果萨勃机组在心肺复苏中的有效率明显高于徒手心肺复苏组,差异有统计学意义（P〈0.05）,但对患者的存活率无明显优势（P〉0.05）。结论 1007型THUMPER心肺复苏机在心肺复苏抢救中有效率得到提高,值得临床推广。     

24-hour Pattern in Lag Time of Response by Firemen to Calls for Urgent Medical Aid

The aim of the study was to assess the group 24-h pattern of lag time (LT) in response by regular and volunteer firemen (RFM and VFM) to calls for medical help (CFMH), specifically calls for out-of-hospital cardiac arrest (OHCA). LT, duration in min between a CFMH and departure of service vehicle equipped with a semiautomated defibrillator and generally staffed with four well-trained and ready-to-go FM, represents the integrated duration of several processes, each with separate reaction and decision-making times. The exact time of each CFHM (in min, h, day, month, yr) was recorded electronically, and the exact departure time from the station of the responding FM vehicle was recorded by an on-duty FM. Overall, CFMH made up 53?±?9% (SEM) of all emergencies calls for aid. To standardize the study methods, the reported findings are based on 568 CFMH specifically regarding OHCA that occurred during the 4-yr study span (January 2005 to December 2008). CFMH exhibited a 24-h pattern with a major peak at 10:00?h (mean?±?SEM: n?=?9.5?±?1.6) and major trough at 01:00?h (n?=?1.3?±?0.3; t test, p?<?.001). From year to year and season to season, a 24-h pattern was detected in the total of CFMH/h with two peaks (～10:00 and ～17:00h) and two troughs (～01:00 and ～15:00?h) (analysis of variance [ANOVA], p?<?.01; Cosinor, p?<?.05 to?<?.003), with neither season- nor year-related differences (χ², p?>?.05). In CFMH/h pooled time series, ANOVA-detected differences between the hourly means (p?<?.01), and Cosinor analysis validated a 24-h rhythm (p?<?.002). In raw data, the longest LT, indicative of poorest performance, occurred at 05:00?h (8.8?±?0.7?min) and the trough of LT, indicative of best performance, at 16:00?h (4.3?±?0.8?min (t test, p?<?.02). 24-h patterning in LT was validated both by ANOVA of hourly means (p?<?.0006) and Cosinor analysis (p?<?.05), with longest LT ～05:00?h and shortest LT ～16.00?h for data of the individual yearly time-series data. The 24-h LT rhythm was also validated in the pooled time series by Cosinor (p?<?.0001), with the 24-h mean?±?SEM?=?6?±?0.17?min and acrophase (peak) of 03:00?h?±?88?min (SD). Curve patterns of CFMH/h and LT/h differed widely. As a group phenomenon, the LT 24-h rhythm mimics the 24-h pattern of performance, as demonstrated by many laboratory and field investigations. The stability of the LT rhythm between years and seasons and its weak relationship with the CFMH 24-h pattern favors the hypothesis of an endogenous component or origin. The nighttime trough of performance is presumably linked to the elevated risk of work accidents in the same population of FM.     

Change in myocardial function after resuscitated sudden cardiac arrest and its impact on long-term mortality and defibrillator implantation

BackgroundThe impact of left ventricular ejection fraction (LVEF) changes after sudden cardiac arrest (SCA) on implantable defibrillator (ICD) utilization and long-term survival is not known. We therefore evaluated the influence of LVEF on these parameters in SCA survivors.MethodsData were collected on consecutive SCA survivors who had ≥1 echocardiogram after SCA and who survived to hospital discharge (n = 655). The median time from baseline to first follow-up echocardiogram was 162 days. LVEF ≥50% was defined as normal. Patients were classified into 4 groups according to baseline (LVEFb) and follow-up (LVEFf) myocardial function: normal LVEFb and LVEFf (group1, n = 261); reduced LVEFb and normal LVEFf (group 2, n = 104); normal LVEFb but reduced LVEFf (group 3, n = 41); and reduced LVEFb and LVEFf (group 4, n = 249). All-cause mortality and time to ICD implantation were examined in all groups.ResultsOver a median follow up of 4.3 years, death occurred in 279 (42%) of patients. Compared with patients in group 1, patients with any reduced LVEF at any time (groups 2–4) had significantly higher mortality, even after adjusting for unbalanced covariates (HR = 1.44, 95.0% CI 1.05–1.95, p = 0.022). ICDs were most commonly implanted in patients with persistently reduced LVEF (group 4: HR = 1.72, 95% CI = 1.26–2.35, p = 0.001).ConclusionWe demonstrate that, in survivors of SCA, a reduced LVEF at or after the index event is associated with higher mortality but that patients with persistently reduced LVEF were most likely to receive ICD therapy. These findings have implications on the management of SCA survivors.     

Ras family proteins: new players involved in the diplotene arrest of Xenopus oocytes

Oogonia undergo numerous mitotic cell cycles before completing the last DNA replication and entering the meiotic prophase I. After chromosome pairing and chromatid exchanges between paired chromosomes, the oocyte I remains arrested at the diplotene stage of the first meiotic prophase. Oocyte growth then occurs independently of cell division; indeed, during this growth period, oocytes (4n DNA) are prevented from completing the meiotic divisions. How is the prophase arrest regulated? One of the players of the prophase block is the high level of intracellular cAMP, maintained by an active adenylate cyclase. By using lethal toxin from Clostridium sordellii (LT), a glucosyl-transferase that glucosylates and inactivates small G proteins of the Ras subfamily, we have shown that inhibition of either Ras or Rap or both proteins is sufficient to release the prophase block of Xenopus oocytes in a cAMP-dependent manner. The implications of Ras family proteins as new players involved in the prophase arrest of Xenopus oocytes will be discussed here.     

Self-incompatibility in Acacia retinodes: Site of pollen-tube arrest is the nucellus

In self-incompatible Acacia retinodes Schldl. var. uncifolia J.M. Black there is no inhibition of self pollen tubes before entry into the ovule, but the frequency of fertilized embryo sacs observed after self pollination is only 0.09–0.24 of that observed after outcrossing. Fluorescence- and light-microscope studies of sectioned, squashed or cleared whole ovules indicate that most self pollen tubes are arrested within the first or second layer of cells of the nucellus. The probability that nucellar arrest represents a primitive feature of self-incompatibility is discussed.     

Changes in the fluctuation of the contraction rhythm of spontaneously beating cardiac myocytes in cultures with and without cardiac fibroblasts

The heart functions as a syncytium of cardiac myocytes and surrounding supportive non-myocytes such as fibroblasts. There is a possibility that a variety of non-myocyte-derived factors affect the maturation of cardiac myocytes in the development of the heart. Cultured neonatal cardiac myocytes contract spontaneously and cyclically. The fluctuation of beating rhythm varies depending on the strength of coupling through gap junctions among cardiac myocytes, indicating that the development of intercellular communication via gap junctions is crucial to the stability of contraction rhythm in cardiac myocytes. In this study, we aimed at elucidating whether and how cardiac fibroblasts affect the development of cardiac myocytes from the point of view of the changes in the fluctuation of the contraction rhythm of cardiac myocytes in cardiac myocyte–fibroblast co-cultures. The present study suggested that cardiac fibroblasts co-cultured with cardiac myocytes enhanced the intercellular communication among myocytes via gap junctions, thereby stabilizing the spontaneous contraction rhythm of cultured cardiac myocytes.     

Association of plasma neutrophil gelatinase-associated lipocalin with acute kidney injury and clinical outcome in cardiac arrest survivors depends on the time of measurement

Purpose: The optimal timing for measurement of neutrophil gelatinase-associated lipocalin (NGAL) level to predict acute kidney injury (AKI) and prognosis in cardiac arrest (CA) survivors has not been elucidated. We aimed to compare the diagnostic and prognostic performance of NGAL levels after return of spontaneous circulation (ROSC) and at 48?h after CA.

Methods: We included 231 adult cardiac arrest survivors who underwent targeted temperature management between May 2013 and December 2016. The primary outcome was stage 2 and 3 AKI (high stage AKI), and the secondary outcomes were in-hospital mortality and neurologic outcome. Sixty-one (26.4%) developed high stage AKI, 50 (21.6%) died, and 152 (65.8%) had a poor neurologic outcome.

Results: NGAL level at 48?h (0.876; 95% confidence interval [CI], 0.826–0.916) had a higher area under receiver operating characteristic curve than NGAL level after ROSC (0.694; 95% CI, 0.631–0.753). Both NGAL levels were independently associated with high stage AKI. NGAL level at 48?h (1.001; 95% CI, 1.000–1.002) remained a significant predictor for in-hospital mortality, while neither of the NGAL levels were independently associated with neurologic outcome.

Conclusions: NGAL at 48?h after CA seems to be a robust predictor for high stage AKI and in-hospital mortality.     

The redistribution of cardiac output in the dog during heat stress

In conscious Greyhound dogs, radioactive microsphere techniques have been used to measure cardiac output, its regional distribution, and proportion of the cardiac output passing through arteriovenous anastomoses (AVA's) in a thermoneutral environment and during severe heat stress. Heat stress resulted in a 74% increase in cardiac output and 4–6% of the cardiac output passed through AVA's. compared with about 1% under thermoneutral conditions: blood flow rate increased in skin of the lower legs and ears, tongue, maxillo turbinals, nasal mucosa, respiratory muscles and spleen, decreased in the thyroids, brain and spinal cord, and did not change significantly in the non-respiratory muscles, heart, pituitary, adrenals, kidneys, liver, stomach and intestines. Thus the circulatory requirements of the heat stressed dogs were met partly by an increase in cardiac output and partly by changes in its distribution. In contrast, the Merino sheep meets such a situation entirely by a redistribution of cardiac output. The present results may be taken as evidence that the Greyhound dog is less heat tolerant than the Merino sheep. The decreased brain blood flow during heat stress is similar to that which occurs in the sheep, but contrast with previous results obtained on anaestherized dogs. The less marked redistribution of cardiac output in the dog compared with the sheep, may explain the apparent difference in energy cost of panting in the two species.     

Risk stratification for sudden cardiac death in hypertrophic cardiomyopathy: Dutch cardiologists and the care of mutation carriers

Background. Patients with hypertrophic cardiomyopathy (HCM) and HCM mutation carriers are at risk of sudden cardiac death (SCD). Both groups should therefore be subject to regular cardiological testing – including risk stratification for SCD – according to international guidelines. We evaluated Dutch cardiologists' knowledge of and adherence to international guidelines on risk stratification and prevention of SCD in mutation carriers with and without manifest HCM. Methods. A questionnaire was sent to 1109 Dutch cardiologists (in training) containing case-based questions. Results. The response rate was 21%. Own general knowledge on HCM care was rated as insufficient by 63% of cardiologists. The percentage of correct answers (i.e. in agreement with international guidelines), on the case-based questions ranged from 37 to 96%, being lowest in cases with an unknown number of risk factors for SCD. A substantial portion of correct answers was based on the correct answer ‘ask an expert opinion’. Significantly more correct answers were provided in cases with manifest HCM. There was little difference between the answers of cardiologists with different self-reported levels of knowledge, with different numbers of HCM patients in their practice or with different numbers of carriers without manifest HCM. Conclusion. Knowledge on risk stratification and preventive therapy was mediocre, and knowledge gaps exist, especially on HCM mutation carriers without manifest disease. Fortunately, experts are frequently asked for their opinion which might bring patient care to an adequate level. Hopefully, our results will stimulate cardiologists to follow developments in this field, thereby increasing quality of care for HCM patients and mutation carriers. (Neth Heart J 2009:17:464–9.).     

Meckel the Younger and his epistemology of organic form: Morphology in the pre-Gegenbaurian age

Summary The goal of our paper is to investigate Meckel’s epistemology of organic form, based on study of his original publications. Johann Friedrich Meckel the Younger (1781–1833) was one of the leading figures of German morphology in the early 19th century. Historiographic studies on morphology in this time period show, that biological research was largely preoccupied with questions about the relationship between form and function. Investigations into Meckel’s epistemology of organic form can contribute to our understanding of the development of morphology in the pre-Gegenbaurian age.     

Modulation of cardiac troponin C function by the cardiac-specific N-terminus of troponin I: influence of PKA phosphorylation and involvement in cardiomyopathies

The cardiac-specific N-terminus of cardiac troponin I (cTnI) is known to modulate the activity of troponin upon phosphorylation with protein kinase A (PKA) by decreasing its Ca²⁺ affinity and increasing the relaxation rate of the thin filament. The molecular details of this modulation have not been elaborated to date. We have established that the N-terminus and the switch region of cTnI bind to cNTnC [the N-domain of cardiac troponin C (cTnC)] simultaneously and that the PKA signal is transferred via the cTnI N-terminus modulating the cNTnC affinity toward cTnI_147-163 but not toward Ca²⁺. The K_d of cNTnC for cTnI_147-163 was found to be 600 μM in the presence of cTnI_1-29 and 370 μM in the presence of cTn1_1-29PP, which can explain the difference in muscle relaxation rates upon the phosphorylation with PKA in experiments with cardiac fibers. In the light of newly found mutations in cNTnC that are associated with cardiomyopathies, the important role played by the cTnI N-terminus in the development of heart disorders emerges. The mutants studied, L29Q (the N-domain of cTnC containing mutation L29Q) and E59D/D75Y (the N-domain of cTnC containing mutation E59D/D75Y), demonstrated unchanged Ca²⁺ affinity per se and in complex with the cTnI N-terminus (cTnI_1-29 and cTnI_1-29PP). The affinity of L29Q and E59D/D75Y toward cTnI_147-163 was significantly perturbed, both alone and in complex with cTnI_1-29 and cTnI_1-29PP, which is likely to be responsible for the development of malfunctions.     

Involvement of oxygen free radicals in the respiratory uncoupling induced by free calcium and ADP-magnesium in isolated cardiac mitochondria: Comparing reoxygenation in cultured cardiomyocytes

Recently, we have observed that the simultaneous application of free calcium (fCa) and ADP-magnesium (Mg) reduced the ADP:O ratio in isolated cardiac mitochondria. The uncoupling was prevented by cyclosporin A, an inhibitor of the permeability transition pore. The purpose of this study was to know if the generation of oxygen free radicals (OFR) is involved in this phenomenon and if it occurs during reoxygenation (Reox) of cultured cardiomyocytes. Cardiac mitochondria were harvested from male Wistar rats. Respiration was assessed in two media with different fCa concentrations (0 or 0.6 M) with palmitoylcarnitine and ADP-Mg as respiration substrates. The production of Krebs cycle intermediates (KCI) was determined. Without fCa in the medium, the mitochondria displayed a large production of citrate + isocitrate + -ketoglutarate. fCa drastically reduced these KCI and promoted the accumulation of succinate. To know if OFR are involved in the respiratory uncoupling, the effect of 4OH-TEMPO (250 M), a hydrosoluble scavenger of OFR, was tested. 4OH-TEMPO completely abolished the fCa- and ADP-Mg-induced uncoupling. Conversely, vitamin E contributed to further decreasing the ADP:O ratio. Since no hydrosoluble electron acceptor was added in our experiment, the oxygen free radical-induced oxidized vitamin E was confined near the mitochondrial membranes, which should reduce the ADP:O ratio by opening the permeability transition pore. The generation of OFR could result from the matrix accumulation of succinate. Taken together, these results indicate that mitochondrial Ca uptake induces a slight increase in membrane permeability. Thereafter, Mg enters the matrix and, in combination with Ca, stimulates the isocitrate and/or -ketoglutarate dehydrogenases. Matrix succinate favors oxygen free radical generation that further increases membrane permeability and allows respiratory uncoupling through proton leakage. To determine whether the phenomenon takes place during Reox, cultured cardiomyocytes were subjected to hypoxia and Reox. ¹⁴C-palmitate was added during Reox to determine the KCI profile. Succinate had not increased during Reox. In conclusion, calcium- and ADP-Mg-induced respiratory uncoupling is due to oxygen free radical generation through excess matrix accumulation of succinate. The phenomenon does not occur during reoxygenation because of a total restoration of mitochondrial magnesium and/or ADP concentration.     

Maternal Coordination of the Daily Rhythm of Malate Dehydrogenase Activity in Testes from Young Rats: Effect of Maternal Sympathetic Denervation of the Pineal Gland and Administration of Melatonin

Chronic sympathetic denervation of the pineal gland by bilateral removal of the superior cervical ganglia (SCG) was performed on female rats 30 days before impregnation. The offspring, maintained in the dark from birth, had disruption of the malate dehydrogenase circadian rhythm in the testes at 25 days of age. A daily injection of melatonin (1 mg/kg s.c. at 10:00 or 18:00 h) to denervated mothers from the 14th day of pregnancy up to the 10th day postpartum produced one daily phase in the enzyme activity of testes in the offspring. Entrainment of daily enzyme activity also was obtained when the hormone was administered orally to the pups during the postnatal period or when pups were reared by intact (not denervated) foster mothers. The results indicate the involvement of the maternal pineal gland in the maternal transfer of photoperiodic information necessary for the coordination of the circadian system in young rats.     

Angiotensin II induces phosphatidic acid formation in neonatal rat cardiac fibroblasts: Evaluation of the roles of phospholipases C and D

Phosphatidic acid has been proposed to contribute to the mitogenic actions of various growth factors. In³²P-labeled neonatal rat cardiac fibroblasts, 100 nM [Sar¹]angiotensin II was shown to rapidly induce formation of³²P-phosphatidic acid. Levels peaked at 5 min (1.5-fold above control), but were partially sustained over 2 h. Phospholipase D contributed in part to phosphatidic acid formation, as³²P- or³H-phosphatidylethanol was produced when cells labeled with [³²P]H₃PO₄ or 1-O-[1,2-³H]hexadecyl-2-lyso-sn-glycero-3-phosphocholine were stimulated in the presence of 1% ethanol. [Sar¹]angiotensin II-induced phospholipase D activity was transient and mainly mediated through protein kinase C (PKC), since PKC downregulation reduced phosphatidylethanol formation by 68%. Residual activity may have been due to increased intracellular Ca²⁺, as ionomycin also activated phospholipase D in PKC-depleted cells. Phospholipase D did not fully account for [Sar¹]angiotensin II-induced phosphatidic acid: 1) compared to PMA, a potent activator of phospholipase D, [Sar¹]angiotensin II produced more phosphatidic acid relative to phosphatidylethanol, and 2) PKC downregulation did not affect [Sar¹]angiotensin II-induced phosphatidic acid formation. The diacylglycerol kinase inhibitor R59949 depressed [Sar¹]angiotensin II-induced phosphatidic acid formation by only 21%, indicating that activation of a phospholipase C and diacylglycerol kinase also can not account for the bulk of phosphatidic acid. Thus, additional pathways not involving phospholipases C and D, such asde novo synthesis, may contribute to [Sar¹]angiotensin II-induced phosphatidic acid in these cells. Finally, as previously shown for [Sar¹]angiotensin II, phosphatidic acid stimulated mitogen activated protein (MAP) kinase activity. These results suggest that phosphatidic acid may function as an intracellular second messenger of angiotensin II in cardiac fibroblasts and may contribute to the mitogenic action of this hormone on these cells. (Mol Cell Biochem141: 135–143, 1994)Abbreviations DAG diacylglycerol - DMSO dimethyl sulfoxide - lysoPC 1-O-hexadecyl-2-lyso-sn-glycero-3-phosphocholine - NRCF newborn rat cardiac fibroblasts - PA phosphatidic acid - PAPase phosphatidic acid phosphohydrolase - PC phosphatidylcholine - PEt phosphatidylethanol - PI phosphatidylinositol - PL (labeled) phospholipids - PLC phospholipase C - PLD phospholipase D Drs. G. W. Booz and M. M. Taher contributed equally to the work described here.     

Maternal Coordination of the Daily Rhythm of Malate Dehydrogenase Activity in Testes from Young Rats: Effect of Maternal Sympathetic Denervation of the Pineal Gland and Administration of Melatonin

Chronic sympathetic denervation of the pineal gland by bilateral removal of the superior cervical ganglia (SCG) was performed on female rats 30 days before impregnation. The offspring, maintained in the dark from birth, had disruption of the malate dehydrogenase circadian rhythm in the testes at 25 days of age. A daily injection of melatonin (1 mg/kg s.c. at 10:00 or 18:00 h) to denervated mothers from the 14th day of pregnancy up to the 10th day postpartum produced one daily phase in the enzyme activity of testes in the offspring. Entrainment of daily enzyme activity also was obtained when the hormone was administered orally to the pups during the postnatal period or when pups were reared by intact (not denervated) foster mothers. The results indicate the involvement of the maternal pineal gland in the maternal transfer of photoperiodic information necessary for the coordination of the circadian system in young rats.     

Regulation of the mitochondrial ATPasein situ in cardiac muscle: Role of the inhibitor subunit

The mitochondrial F₁-ATPase inhibitor protein, IF₁, binds to subunits of the F₁-ATPase bothin vitro andin situ under nonenergizing conditions, i.e., under conditions that allow a net hydrolysis of ATP by the mitochondrial ATPase to take place. This reversible IF₁ binding occurs in a wide variety of cell types including (anaerobic) baker's yeast cells and (ischemic) mammalian cardiomyocytes under conditions that limit oxidative phosphorylation. The binding of inhibitor results in a marked slowing of ATP hydrolysis by the undriven mitochondrial ATP synthase. An apparent main function of this reversible IF₁ binding, at least in cells that undergo aerobic-anaerobic switching, is the mitigation of a wasteful hydrolysis of ATP produced by glycolysis during anoxic or ischemic intervals, by the mitochondrial ATPase. While this apparent main function is probably of considerable importance in cells that normally either can or must undergo aerobic-anaerobic switching such as baker's yeast cells and skeletal myocytes, one wonders why a full complement of IF₁ has been retained in certain cells that normally do not undergo such aerobic-anaerobic switching, cells such as adult mammalian cardiomyocytes of many species. While some mammalian species have, indeed, not retained a functional complement of IF₁ in their cardiomyocytes, those that have can benefit significantly from its presence during intervals of myocardial ischemia.This mini-review is dedicated to the memory of Professor Efraim Racker.     

Neural crest origin of cardiac ganglion cells in the chick embryo: Identification and extirpation

Using interspecific grafting of neural crest between quail and chick embryos, it was determined that the cardiac ganglia originate from the cranial region (somites 1–2) of the vagal neural crest (somites 1–7). Neuronal uptake of [³H]choline was used as an index of neuronal development in the chick atrium. Normal uptake was found to be quite high between Days 8 and 14 of incubation. Following extirpation of neural crest over somites 1 to 3 at stages 8 to 10, neuronal uptake in 8-day chick atrium was decreased by 25–60% depending on the stage at which the lesion was performed. It is thought that the residual uptake represents preganglionic terminals from the dorsal motor nucleus of the vagus. Embryos with extirpations of neural crest over somites 1–3 performed at stage 9 showed the greatest decrease of neuronal choline uptake and did not live beyond 11 days of incubation. However, hearts from embryos with partial lesions (performed at stage 10) were treated on incubation Days 12 and 15 for demonstration of acetylcholinesterase in the subepicardial plexus. These hearts showed much less extensive neural plexus with sparse, small cardiac ganglia.